Method, system and use for therapeutic ultrasound

ABSTRACT

The described embodiments relate to methods, systems and uses for therapeutic ultrasound, and in particular, to methods, systems and uses for therapeutic ultrasound and contact lenses for treating or alleviating eye conditions. The described embodiments relate to methods, systems and uses that involve an ultrasound device configured for treatment of an eye condition and a contact lens protects ocular tissue of the eye and forms a chamber of air.

FIELD

The described embodiments relate to methods, systems and uses fortherapeutic ultrasound, and in particular, to methods, systems and usesfor therapeutic ultrasound for treating or alleviating eye conditions.

INTRODUCTION

Eye conditions may relate to meibomian gland dysfunction. Dry eye is amultifactorial disease of epidemic proportions. Dry eye may be caused bymeibomian gland dysfunction. Dry eye can be categorized into two broadcategories: aqueous deficient dry eye and evaporative dry eye. Withblockage of the eyelid meibomian glands and ducts there may be areduction of lipids within the tear film. This results in instability ofthe tear film with subsequent early tear break up and evaporation. Thisultimately leads to exposure of the corneal surface and a cascade ofocular surface inflammation, thus perpetuating a dysfunctional tearsyndrome.

Another example eye condition is a chalazion or meibomian cyst which isa collection of oil or blockage of the meibomian gland and ducts. Afurther example of an eye condition is a hordeolum or stye which may bean inflamed sebaceous gland of Zeiss. Finally, an additional example isblepharitis which is an inflammation of the eyelid which may predisposesubjects to aforementioned eye conditions, such as dry eye, chalazion,hordeolum. Other eye conditions include scarring.

There is a need for improved methods, systems and uses for treating oralleviating eye conditions, such as those associated with the meibomiangland and ducts, or at least alternatives.

SUMMARY

In a first aspect, embodiments described herein relate to an ultrasounddevice and air gap lens for treatment of an eye condition.

Embodiments may include a contact lens with internal air chamber and thetransducer may be applied externally through the eyelid. This may enablea longer transducer length to cover the entire length of the meibomianglands. The external transducer may also be able to move along theentire length of the meibomian glands.

The internal air gap and lens may impede ultrasound gel or water gettinginto the air gap. Ultrasound gel may get under the contact lens andirritate the eye.

The shape of the contact lens may vary, and in some example embodimentsmay be elliptical to maximize the number of meibomian glands treatedacross the full horizontal length of the eyelid.

In some embodiments, drug delivery (e.g. steroid) may be facilitated bythe ultrasound use. This may be referred to as phonophoresis.

In some embodiments, an imaging device may be used or a dual transducercould treat and image. The imaging and processing may quantify theamount of meibum in the glands and ductules. Post treatment imaging mayshow a reduction of meibum in the glands thus confirming that the oilwas expressed.

The device may include at least one ultrasound transducer for supplyingultrasound waves to an area proximate to the portion of the eyelidaccording to treatment parameters. The ultrasound transducer may providetherapeutic ultrasound generally across the frequency range 0.2 to 10MHz according to some embodiments. In other embodiments the frequencyrange may extend as high as 50 MHz One example mechanism for therapeuticgain may be differential absorption of ultrasound in fats compared tonon-fatty tissues. This increases with increasing frequency which maysupport a higher frequency range.

These illustrative frequency ranges are not intended to restrict.Therapeutic Ultrasound may be generally applied across various frequencyranges.

The air gap lens may be used to protect ocular tissue around the eye.The lens may be a vaulted scleral contact lens configured for placementover the eye globe and under the eyelid. The lens may have two layers ormay comprise two lenses configured to form a chamber of air between thelayers or lenses. The chamber of air may protect the cornea and mayblock penetration of ocular tissue by the ultrasound waves.

The closed air chamber within the lens structure may ensure that thereis always a built-in air barrier to ultrasound which may providesufficient acoustic impedance. With such a design ultrasound contact gelcan be used on the surface of the eyelid or periocular tissue withoutconcern of the gel or any other fluid getting into the air barrier. Asultrasound does not propagate well through gases this design wouldprovide high acoustic impedance and thus shield the eye from ultrasoundenergy. The different layers of the lens may also comprise an absorptivematerial to block penetration of ocular tissue by the ultrasound waves.In particular, if the ultrasound is being applied externally through aseparate ultrasound probe, then outer surface of the contact lens whichabuts the tarsal conjunctiva of the eyelid could be made of anabsorptive material or have an absorptive coating hat would uniformlyheat and further act to warm the inner eyelid and the meibomian glands.

The lens could be circular. Alternatively it could be an ellipticalshape to conform to the full horizontal length of the tarsal platewithin which the meibomian glands are situated. Similarly the PZTtransducer whether built into the contact lens or applied externallythrough a separate probe could be an elliptical shape or other similarshape which would allow simultaneous irradiation of the maximum numberof meibomian glands in both the upper and lower eyelids.

In some embodiments, the system may further comprise a lens speculum toelevate the eyelid from the eye globe and create airspace between eyeglobe and eyelid.

In some embodiments, the system may further comprise a temperaturemeasurement mechanism for measuring the temperature of the areaproximate to the portion of the eyelid. In some embodiments, thetemperature measurement mechanism may comprise a thermal couple or othercomparable thermal measuring device. In some embodiments, the thermalcouple may be positioned on the contact lens. In some embodiments, thesystem may further comprise an ultrasound measurement mechanism formeasuring the ultrasounds waves at the area proximate to the portion ofthe eyelid.

In some embodiments, the treatment parameters comprise a frequency,amplitude, on/off cycle, and a treatment period. In some embodiments,the treatment frequency is at least 2 MHz, at least 3 MHz, or between 3to 5 MHz, or higher than 5 MHz The treatment frequency may range 0.2 to10 MHz according to some embodiments. In other embodiments the frequencyrange may extend as high as 50 MHz. One example mechanism fortherapeutic gain may be differential absorption of ultrasound in fatscompared to non-fatty tissues. This increases with increasing frequencywhich may support a higher frequency range. In some embodiments, thetreatment period is between two to five minutes. The treatment timecould however be increased to 10 to 15 minutes if a more gradual andprolonged heating was desired. These are non-limiting examples.

The on/off cycle may be used to pulse the ultrasound waves.

In some embodiments, the device further comprises a controller operablefor receiving treatment data, determining the treatment parameters basedon the treatment data, and directing the ultrasound transducer accordingto the treatment parameters.

In some embodiments, the eye condition is caused by dysfunction of themeibomian glands and wherein the area proximate to the portion of theeyelid comprises the meibomian glands and its ductules. In someembodiments, the eye condition is caused by dysfunction of the lacrimalglands and wherein the area proximate to the portion of the eyelidcomprises the lacrimal glands and ductules. In some embodiments, the eyecondition is caused by dysfunction of the periocular glands and whereinthe area proximate to the portion of the eyelid comprises the periocularglands and ductules. In some embodiments, the eye condition is caused bydysfunction of the nasolacrimal system and wherein the area proximatecomprises the nasolacrimal system. In some embodiments, the eyecondition is caused by dysfunction of the Wolfring glands and whereinthe area proximate to the portion of the eyelid comprises the Wolfringglands and ductules. In some embodiments, the eye condition is caused bydysfunction of the Krause glands and wherein the area proximate to theportion of the eyelid comprises the Krause glands and ductules. In someembodiments, the eye condition is caused by dysfunction of the Zeisglands and wherein the area proximate to the portion of the eyelidcomprises the Zeis glands and ductules.

In some embodiments, the eye condition is caused by lipids blocked inone or more glands of the eye and wherein the ultrasound waves heat thelipids to emulsify the lipids blocked in the glands and ductules andfacilitate flow. In some embodiments, the ultrasound waves heat thelipids to approximately 40 degrees Celsius to increase flow and mobilityof the lipids. This is a non-limiting example. In some embodiments, theultrasound waves supply oscillations to move the emulsified lipids bycreating bubbles in the emulsified lipids. In some embodiments, theultrasound waves supply acoustic streaming to mobilize the emulsifiedlipids. In some embodiments, the ultrasound waves cause microcavitationto mobilize the emulsified lipids. In some embodiments, the ultrasoundwaves stimulate circulation and lymph flow in the area proximate to theportion of the eyelid.

In some embodiments, the ultrasound waves breakdown scar tissue in thearea proximate to the portion of the eyelid.

In some embodiments, the ultrasound waves supply continuous ultrasoundenergy. In some embodiments, the ultrasound waves supply pulsedultrasound energy defined by on/off cycle.

In some embodiments, the device further comprises a probe for couplingto the ultrasound transducer.

In some embodiments, the device is configured to provide phased arrayultrasound to vary ultrasound waves.

In some embodiments, the ultrasound transducer comprises movablecomponents that are configured to move relative to the portion of theeyelid to vary ultrasound waves.

In some embodiments, the device comprises an ultrasound imaging cameraand wherein the device is operable in a therapeutic mode to heat thearea proximate to the portion of the eyelid and a diagnostic mode toimage the area proximate to the portion of the eyelid using theultrasound imaging camera. In some embodiments, the device can operatein therapeutic mode and diagnostic mode to perform real-time imagingduring treatment.

In some embodiments, an imaging device may be used or a dual transducercould treat and image. The imaging and processing may quantify theamount of meibum in the glands and ductules. Post treatment imaging mayshow a reduction of meibum in the glands thus confirming that the oilwas expressed.

In some embodiments, the ultrasound transducer has a concave shape tocomplement the eyelid, or the ultrasound transducer has an attachmentwith a concave shape to complement the eyelid. In some embodiments, theultrasound transducer has an elliptical shape to complement the eyelid.In some embodiments, the device further comprises an attachment for theultrasound transducer, wherein the attachment comprises a protectiveportion for positioning over the eye globe and under the eyelid toprotect eye tissue, wherein the protective portion has a concave shapeto complement the eyelid.

In some embodiments, the eye condition is selected from the groupconsisting of dry eye, meibomian gland dysfunction, duct dysfunction,lacrimal gland dysfunction, periocular gland dysfunction, nasolacrimalsystem dysfunction, post-surgical scarring, and chalazion.

In another aspect, embodiments described herein provide use of anultrasound device configured for treatment of dry eye, wherein thedevice comprises at least one ultrasound transducer for coupling to atleast a portion of an eyelid to supply ultrasound waves to an areaproximate to the lacrimal glands to stimulate aqueous production andflow from the lacrimal glands and ducts.

In another aspect, embodiments described herein provide the use of ahigh frequency ultrasound device configured for treatment of dry eye,wherein the device comprises at least one ultrasound transducer forcoupling to at least a portion of an eyelid to supply ultrasound wavesto an area proximate to the meibomian gland to stimulate meibumproduction and flow from the meibomian gland and ducts.

In a further aspect, embodiments described herein provide a system fortreating an eye condition comprising: an ultrasound device comprising atleast one ultrasound transducer for coupling to at least a portion of aneyelid to supply ultrasound waves to an area proximate to the portion ofthe eyelid according to treatment parameters. In some embodiments, thetreatment parameters comprise a frequency, an amplitude, on/off cycle,and a treatment period. Example frequency ranges include 0.2 to evenhigher than 50 MHZ, other examples may be at least 2 MHz, at least 3MHz, and between 3 to 5 MHZ. Greater than 5 MHZ frequencies may also beused to limit depth of penetration into tissue. An example treatmentperiod is between two to five minutes. Further example frequency rangesinclude 0.2 to 10 MHz according to some embodiments. In otherembodiments the frequency range may extend as high as 50 MHz. Oneexample mechanism for therapeutic gain may be differential absorption ofultrasound in fats compared to non-fatty tissues. This increases withincreasing frequency which may support a higher frequency range. Theseare non-limiting examples.

In some embodiments, the system further comprises a controller operablefor receiving treatment data from an external source, determining thetreatment parameters based on the treatment data, and directing theultrasound transducer according to the treatment parameters.

In some embodiments, the ultrasound waves heat the area proximate to theportion of the eyelid.

In some embodiments, the eye condition is caused by lipids blocked in agland or duct of the eye and wherein the ultrasound waves heat the areaproximate to the portion of the eyelid to emulsify the lipids blocked inthe gland or the duct and facilitate flow. In some embodiments, theultrasound waves heat the lipids to approximately 40 degrees Celsius oreven higher. In some embodiments, the ultrasound waves supplyoscillations to move the emulsified lipids by creating bubbles in theemulsified lipids. In some embodiments, the ultrasound waves supplyacoustic streaming to mobilize the emulsified lipids. In someembodiments, the ultrasound waves cause microcavitation to mobilize theemulsified lipids. In some embodiments, the ultrasound waves stimulatecirculation and lymph flow in the area proximate to the portion of theeyelid. In some embodiments, the ultrasound waves breakdown scar tissuein the area proximate to the portion of the eyelid. In some embodiments,the ultrasound waves supply continuous ultrasound energy. In someembodiments, the ultrasound waves supply pulsed ultrasound energy.

In some embodiments, the device further comprises a probe for couplingto the ultrasound transducer. In some embodiments ultrasound gel can beused as a contact medium between the eyelid and the ultrasoundtransducer. In some embodiments, the device is configured to providephased array ultrasound. In some embodiments, the ultrasound transducercomprises movable components that are configured to move relative to theportion of the eyelid to vary ultrasound waves. In some embodiments, thedevice comprises an ultrasound imaging camera and wherein the device isoperable in a therapeutic mode to heat the area proximate to the portionof the eyelid using the ultrasound waves and a diagnostic mode to imagethe area proximate to the portion of the eyelid using the ultrasoundimaging camera. In some embodiments, the ultrasound transducer has aconcave shape to complement the eyelid. In some embodiments, ultrasoundtransducer has an elliptical shape to complement the eyelid. In someembodiments, the device further comprises an attachment for theultrasound transducer, wherein the attachment comprises a protectiveportion for positioning over the eye globe and under the eyelid toprotect eye tissue, wherein the protective portion has a concave shapeto complement the eyelid. In some embodiments, the eye condition isselected from the group consisting of dry eye, meibomian glanddysfunction, duct dysfunction, lacrimal gland dysfunction, perioculargland dysfunction, nasolacrimal system dysfunction, post-surgicalscarring, and chalazion.

In some embodiments, the system may further comprise a roller shaped tocomplement the eyelid and applied to the eyelid to express theemulsified lipids from the gland or the duct. In a further aspect,embodiments described herein provide a method for treating an eyecondition using a therapeutic ultrasound device, the method comprising:coupling at least one ultrasound transducer to at least a portion of aneyelid; and propagating ultrasound waves to an area proximate to theportion of the eyelid using the ultrasound transducer according totreatment parameters.

In some embodiments, the treatment parameters comprise a frequency, anamplitude, on/off cycle, and a treatment period. In some embodiments,the method may further comprise placing a contact lens over the eyeglobe and under the eyelid to protect ocular tissue around the eye. Insome embodiments, the lens is a vaulted scleral contact lens configuredto form a chamber of air. The chamber of air may be between lens layersof different radii of curvature or it may be behind the posteriorsurface of the contact lens and the cornea.

In some embodiments, the lens comprises an absorptive material to blockpenetration of ocular tissue by the ultrasound waves. The chamber of airmay also block penetration of ocular tissue by the ultrasound waves.

In some embodiments, the method may involve using a lens speculum toelevate the eyelid from the eye globe and create an airspace between eyeglobe and eyelid. In some embodiments, the eye condition relates to themeibomian glands and wherein the ultrasound waves are supplied for thetreatment period to liquefy solidified fats in the meibomian glands. Insome embodiments, the eye condition relates to the glands of Zeiss witha hordeolum present and wherein the ultrasound waves are supplied forthe treatment period to liquefy fats in the glands of Zeiss when thehordeolum is present.

In some embodiments, the method may further comprise applying ultrasoundgel to the surface of the eyelid to act as a coupling medium between eyetissue and the transducer.

In another aspect, embodiments described herein provide use of anultrasound device configured for treatment of meibomian glanddysfunction caused by solidified fats, wherein the device comprises atleast one ultrasound transducer for coupling to at least a portion of aneyelid to supply ultrasound waves to the meibomian glands and ductulesto heat the meibomian glands and ductules and liquefy the solidifiedfats.

In another aspect, embodiments described herein provide use of anultrasound device configured to promote remodeling and resolution ofeyelid scar tissue from the etiology selected from the group consistingof post-surgical, post chalazion, post-inflammatory, andpost-infectious, wherein the device comprises at least one ultrasoundtransducer for coupling to at least a portion of the eyelid to supplyultrasound waves to breakdown scar tissue in the eyelid. This treatmentcould be combined with topical steroids placed directly on the dermis ofthe eyelid within the coupling medium. The ultrasound energy couldfacilitate steroid penetration into the eyelid tissue and into theperiocular glands, in particular the meibomian glands. Ultrasound couldbe used over the eyelids or meibomian glands to promote drug delivery ofother topical medications through the process of phonophoresis

In a further aspect, embodiments described herein provide the use of anultrasound device configured for treatment of an eye condition, whereinthe device is operable in a therapeutic mode and a diagnostic mode,wherein the device comprises at least one ultrasound transducer forcoupling to at least a portion of an eyelid to supply ultrasound wavesto an area proximate to the portion of the eyelid to diagnose the eyecondition in the diagnostic mode and to treat the eye conditionaccording to treatment parameters in the therapeutic mode.

In some embodiments, the ultrasound device is configured to operate indiagnostic mode and therapeutic mode concurrently to provide real-timeimaging during treatment.

In another aspect, embodiments described herein provide the use of anultrasound device configured to facilitate fluid flow down thenasolacrimal system, wherein the device comprises at least oneultrasound transducer for coupling to at least a portion of an innercanthal region of the eye to supply ultrasound waves to an areaproximate nasolacrimal system according to treatment parameters.

In another aspect, embodiments described herein provide the use of anultrasound device configured to break up stones within the nasolacrimalsystem, wherein the device comprises at least one ultrasound transducerfor coupling to at least a portion of an inner canthal region of the eyeto supply ultrasound waves to an area proximate nasolacrimal systemaccording to treatment parameters, wherein the treatment parameterscomprise a treatment frequency and a treatment period.

DRAWINGS

For a better understanding of embodiments of the systems, methods anduses described herein, and to show more clearly how they may be carriedinto effect, reference will be made, by way of example, to theaccompanying drawings in which:

FIG. 1 shows a diagram of a system for eye conditions using therapeuticultrasound according to some embodiments;

FIG. 2 shows a diagram of a meibomian gland according to someembodiments;

FIG. 3 shows a diagram of a use of therapeutic ultrasound for eyeconditions according to some embodiments;

FIG. 4 shows a diagram of a method using ultrasound for eye conditionsaccording to some embodiments;

FIG. 5 shows another diagram of a use of therapeutic ultrasound for eyeconditions according to some embodiments;

FIG. 6 shows a diagram of a use of therapeutic ultrasound with anattachment for eye conditions according to some embodiments; and

FIG. 7 shows another diagram of a use of therapeutic ultrasound with anattachment for eye conditions according to some embodiments.

FIG. 8 an example external transducer and contact lens to protect theeye according to some embodiments.

FIG. 9 shows an example internal transducer and contact lens to protectthe eye according to some embodiments.

FIG. 10 an example system including a transducer and a contact lens withair gap according to some embodiments.

FIG. 11 an example prototype lens.

FIG. 12 another example system including a transducer and a contact lenswith air gap according to some embodiments.

FIG. 13 illustrates an example thermal model.

FIG. 14 illustrates an example acoustic source model.

FIG. 15 illustrates a chart of temperature rise against time for theexternal transducer configuration.

FIG. 16 illustrates a contact lens area proximate to FSA and ultrasoundgel.

FIG. 17 illustrates a chart of temperature rise against time for FSA.

FIG. 18 illustrates example vacuum molded PVDF to construct sub-tarsaldevices.

FIG. 19 illustrates example prototypes for PZT internal transducers forembedding within air gap contact lens.

FIGS. 20 and 21 illustrate attenuation as a function of frequency.

FIGS. 22 to 25 illustrate example prototypes for PZT internaltransducers for embedding within air gap contact lens.

FIG. 26 illustrates a graph from measured attenuation of porcine eyelid.

FIGS. 27 and 28 illustrate schematics of experimental embodiments.

FIGS. 29 a and 29 b illustrate example graphs of the relative fieldintensities.

FIGS. 30 a and 30 b illustrate examples graphs of heating curves.

FIGS. 31 a, 31 b, 32 a, 32 b, 33 a, 33 b, 36 a and 36 b illustrateexample graphs of temperature curves.

FIGS. 34 a, 34 b, and 35 illustrate example graphs of time curves.

The drawings, described below, are provided for purposes of illustrationof the aspects and features of various examples of embodiments describedherein. For simplicity and clarity of illustration, elements shown inthe figures have not necessarily been drawn to scale. The dimensions ofsome of the elements may be exaggerated relative to other elements forclarity. Further, where considered appropriate, reference numerals maybe repeated among the figures to indicate corresponding or analogouselements.

DESCRIPTION OF VARIOUS EMBODIMENTS

It will be appreciated that numerous specific details are set forth inorder to provide a thorough understanding of the exemplary embodimentsdescribed herein. However, it will be understood by those of ordinaryskill in the art that the embodiments described herein may be practicedwithout these specific details. In other instances, well-known methods,procedures and components have not been described in detail so as not toobscure the embodiments described herein. Furthermore, this descriptionshould be considered as describing implementation of the variousembodiments described herein.

The described embodiments relate to methods, systems and uses fortherapeutic ultrasound for treating or alleviating eye conditions, suchas dry eye and other conditions associated with gland dysfunction andeyelids.

Eye conditions may relate to meibomian gland dysfunction. For example,one of the underlying causes of dry eye may be meibomian glanddysfunction. Other example eye conditions include chalazion, meibomiancysts, hordeolum, stye, blepharitis and so on. Meibomian glanddysfunction may occur due to a variety of factors. These factors rangefrom keratinization of ductules, inflammation of ducts, solidificationof lipid secretions, and atrophy of glands themselves. A meibomian glandblockage, dry eye, and other eye conditions may be ameliorated withheat. The heat required to break up oil secretions involves a treatmentthat sufficiently warms the eyelid for a period of time. For example,heat treatment may warm the eyelids to 40 degrees Celsius for fourminutes. This is an example only and other time periods may be useddepending on temperatures used. Hot water (wet towel) compresses may beused to apply wet heat to the eyelids. Although efficacious, patientcompliance may be a problem and the technique may be error prone as thecompress may not warm eyelids to sufficiently warm temperatures. Asanother treatment approach, a product may heat the eyelids and massagethem to facilitate expression of oil contents. Although efficacious thistreatment product may be costly and a transducer head may have to bepurchased for each patient.

The described embodiments relate to methods, systems and uses fortherapeutic ultrasound for eye conditions by providing heat andoscillatory ultrasound energy to the eyelids, meibomian glands, lacrimalgland, or other glands and areas proximate eye. By using therapeuticultrasound energy the depth of tissue penetration may be minimized whilethe amount of energy delivered to the tissue may be maximized.

For therapeutic ultrasound, the frequency used typically ranges from 0.2to 10 MHz depending on tissue depth penetration. Absorption andtherefore energy deposition increases with increasing frequency. Sincethe eyelid is only several millimeters in thickness a range of differentfrequencies may be used by the described embodiments to heat the eyelidand meibomian glands. The ultrasound transducer may provide therapeuticultrasound generally across the frequency range 0.2 to 10 MHz accordingto some embodiments. In other embodiments the frequency range may extendas high as 50 MHz. Alternatively, a lower frequency therapeuticultrasound may be used at a higher power setting or a longer duration togenerate sufficient heat. The use of therapeutic ultrasound may helpemulsify blocked fats by two distinct example mechanisms. For example,the high frequency ultrasound may provide heat energy to fats in thegland. The heat energy delivered may liquefy solidified fats. Theoscillations would further act to mobilize oil movement through theformation of small bubbles in the oil medium. This may be referred to asmicrocavitation. Accordingly, the use of therapeutic ultrasound may heatthe gland to liquefy fat blockage and create microcavitation.

Ultrasound energy may further facilitate movement of oil within theglands and/or ductules through acoustic streaming. The therapeuticultrasound may also stimulate circulation in the eyelid and meibomiangland, which may promote clearance of inflammatory mediators. Further,the therapeutic ultrasound may help breakdown and remodel scar tissue inthe eyelid, which may be the result of a chalazion, or other trauma orinfection/inflammation to eyelid. Therapeutic ultrasound may be usedpost-surgically on the eyelid to reduce scar formation and facilitatehealing of tissue after eyelid surgery. These eyelid surgeries couldinclude but would not be limited to blepharoplasty, ptosis repair,entropion repair, ectropion repair, excisional and incisional biopsiesand so on. When used to remodel scar tissue therapeutic ultrasound couldbe combined with other treatments such as intralesional injection ofcorticosteroids or topical application of steroids and otheranti-inflammatories. In this situation therapeutic ultrasound mayfacilitate penetration of and distribution of medications through theprocess of phonophoresis. Ultrasound could be used over the eyelids ormeibomian glands to promote drug delivery of other topical medicationsthrough the process of phonophoresis

Alternatively, or in conjunction with being directed on the meibomianglands, ultrasound energy could be directed superotemporally in theorbit to focus energy on the lacrimal gland. This acoustic energy maystimulate secretion of tears from the lacrimal gland through to thelacrimal ducts.

In addition to aforementioned applications of therapeutic ocularultrasound, if the power and frequency settings are varied, ultrasoundenergy may be directed medially at the nasolacrimal duct apparatus toresolve partial and complete blockages. Ultrasound energy can be used toresolve blockages of the upper and lower canalaculi, the lacrimal sac,or the nasolacrimal duct itself. The ultrasound could be used at lowersettings to facilitate flow through the entire apparatus in partialblockages or functional blockages. The ultrasound may be used at higherenergy settings to break up stones if they are obstructing the passages.This technique may be directed to stones located anywhere along theentire course of the nasolacrimal system. This ultrasound method may beanalogous to the lithotripsy used for treatment of kidney stones. Asmall probe attachment may be used for this application as it wouldallow the clinician to focus or broaden ultrasound energy around thedesired location.

Referring now to FIG. 1 there is shown a system using therapeuticultrasound for eye conditions. The system 10 is operable to connect atransducer head 16 to an ultrasound machine 12 via connector 18. Thetransducer head 16 may be shaped to complement various portions of theeye. Further, the transducer head may include a small probe attachmentsized proportional to the portion of the eye to be treated in order tofocus or broaden energy on the specific treatment portion of the eye.

The transducer head 16 may also include a piezoelectric crystal 14 ornumerous crystals as a non-limiting illustrative example. Other exampletransducer heads 16 are electromagnetic transducers, PZT transducers,and so on. This is an example transducer and other types may be used.For example, transducer may be constructed from a piezeoelectric ceramicwith perovskite structure, such as lead zirconate titanate (PZT) itsvarieties. The transducer may also be made from a piezoelectric polymer,such as polyvinylidene fluoride (PVDF) film (or other material) forexample. Piezoceramics may include PZT and PZT-varieties, bariumtitanate, lead titanate, lead zirconate titanate, potassium niobate,lithium niobate, lithium tantalate, sodium tungstate, zinc oxide, and soon.

In this illustrative example, the system 10 is operable to deliverenergy through the ultrasound machine 12 to the transducer head 16coupled to the closed eyelid 24. A gel 20 may be used as a couplingmedium to allow direct contact of the transducer head to the closedeyelid 24. The external transducer may also be able to move along theentire length of the meibomian glands.

Embodiments may include a contact lens with internal air chamber and thetransducer may be applied externally through the eyelid. This may enablea longer transducer length to cover the entire length of the meibomianglands. The internal air gap and lens may impede ultrasound gel or watergetting into the air gap. Ultrasound gel may get under the contact lensand irritate the eye.

The shape of the contact lens may vary, and in some example embodimentsmay be elliptical to maximize the number of meibomian glands treatedacross the full horizontal length of the eyelid.

The ultrasound machine 12 may operate at a varying frequencies dependingon the treatment parameters. For example, a lower frequency at a higherpower (or amplitude) may also be used. The ultrasound transducer mayprovide therapeutic ultrasound generally across the frequency range 0.2to 10 MHz according to some embodiments. In other embodiments thefrequency range may extend as high as 50 MHz. The delivery of ultrasoundenergy may be continuous or pulsed. Pulsed energy may allow for a slowerheat rise than continuous ultrasound energy at the same intensity. Apulsed ultrasound application may take longer to warm the tissue but mayprovide a larger safety margin and reduce chance of tissue burn. This isan example configuration of a system.

In another aspect, there is provided a system for treating an eyecondition comprising an air gap lens and one or more ultrasoundtransducers. The ultrasound transducer may be positioned within or onthe air gap lens, as described herein. FIG. 9 provides an examplerepresentation.

Referring back to FIG. 1, the ultrasound machine 12 is configured fortreatment of an eye condition, such as dry eye, dysfunction of themeibomian gland, lacrimal gland, periocular gland, and nasolacrimalsystem, chalazion, and scarring. The ultrasound transducer 16 is adaptedfor eye treatment and suitable for coupling to at least a portion of aneyelid to supply ultrasound waves to the eyelid according to treatmentparameters. The treatment parameters may include a frequency, anamplitude (e.g. power), an on/off cycle (e.g. for pulses), a phase, anda treatment period. An example treatment frequency range is between 0.2MHz, 10 MHz, up to 50 MHz and further examples are provided herein. Thetreatment parameters may specify a range of frequencies and amplitudesfor the ultrasound waves.

The ultrasound machine 12 may also be connected to a temperaturemeasurement device (e.g. measurement tool 25 of FIG. 5) that isconfigured to measure temperature elevations induced by deposition ofacoustic energy to the eyelid by the ultrasound transducer 16. If thetemperature increases above the range a warning alert may be generatedto adjust the treatment parameters or the transducer 16 may be shut downautomatically to avoid damage to the eye or eyelid. If the temperaturedecreases below the range an alert may be generated to adjust thetreatment parameters. An example temperature measurement device may be athermocouple. A measurement device may also measure ultrasound waves andprovide the measurement data to ultrasound machine 12. If the ultrasoundwaves pass a predetermined safety threshold then the transducer 16 mayautomatically shut down or adjust to stay within the safety threshold.An example measurement device for ultrasound waves is a hydrophone.

The frequency range may provide sufficient ultrasound energy to heat thetreatment area of the eye. For example, the frequency range of 0.2 MHzto 50 MHz or higher may provide sufficient ultrasound energy to heat thetreatment area of the eye to 40 degrees Celsius. Tissue denaturation maystart at temperatures over 43 when applied for long treatment periods,such as over 200 minutes. The treatment period may be proportional tothe treatment frequency, as a lower frequency may require a longerperiod and vice versa. Example treatment periods range between thirtyseconds to twenty minutes, one minute to ten minutes, and two to fiveminutes, or longer depending on the treatment parameters. These arenon-limiting example treatment periods and frequencies and others may beused.

The eye condition may be caused by lipids blocked in a gland of the eyeand the ultrasound waves may heat the treatment area of the eyelid toemulsify the lipids blocked in the gland. As noted herein, theultrasound waves may supply oscillations to move the emulsified lipidsby creating bubbles in the emulsified lipids, may supply acousticstreaming to mobilize the emulsified lipids, may cause microcavitationto mobilize the emulsified lipids, stimulate circulation in the areaproximate to the portion of the eyelid, and breakdown scar tissue in thearea proximate to the portion of the eyelid.

The ultrasound machine 12 may include a controller to receive treatmentdata from a data source (e.g. computing system 32 or other third partynetworked system). The controller may process the treatment data todetermine the treatment parameters and direct the ultrasound transducer16 to propagate ultrasound waves according to the treatment parameters.The treatment data may define eye condition, measurements, location, andso on. The ultrasound machine 12 may also connect to an ultrasoundimaging camera. The ultrasound machine 12 is operable in a therapeuticmode to heat the area proximate to the portion of the eyelid. Theultrasound machine 12 is operable in a diagnostic mode to image the areaproximate to the portion of the eyelid using the ultrasound imagingcamera. The imaging camera could visualize the consolidated meibum inthe meibomian gland and its ductules. It could also quantify the amountof meibum in the glands. A reduction in meibomian gland volume wouldconfirm that oil was expressed out of the glands and ductules Thediagnostic mode may be used to collect treatment data regarding the eyecondition.

The system 10 may also include a roller 26 to express oil secretionsfrom the meibomian glands. The roller 26 may have various shapes, suchas a curve or concave shape to complement the eye.

The piezoelectric crystal 14 may be a PZT-8 or similar material, or mayuse other techniques such as electromagnetic. The ultrasound machine 12may be powered by various means such as by a standard current or aninternal battery. The transducer head 16 may be a plastic materialforming a sealed transducer, a head cover, and so on. The transducerhead 16 may have various shapes and components, such as a curved orconcave shape complementary to eyelid, elliptical shape, a flat head,thin plates extension, probe attachments, and so on. The piezoelectriccrystal 14 may contract and expand based on the ultrasonic frequencysignals supplied by the ultrasound machine 12 to generate ultrasonicpressure waves which are coupled to the closed eyelid 24 via transducer16. Any oscillating component with a transducer head 16 may provideultrasound energy through the probe to the eyelid, meibomian glands,lacrimal gland, periocular glands or nasolacrimal system. Thetransmission of the pressure waves into the closed eyelid 24 may beenhanced by the gel 20. The ultrasonic pressure waves propagate throughthe closed eyelid 24 to the meibomian glands, lacrimal gland, periocularglands or nasolacrimal system.

Transducer 16 may be held in place by an adhesive, a clip, or by ahealth assistant for a treatment period. When the treatment is appliedby a health assistant the probe may be slowly moved over the closedeyelid 24. Moving the transducer head 16 during treatment may beimportant because of the following effects: to smooth out irregularitiesof the near field, to minimize hotspot formation, to reduceirregularities of absorption that might occur due to reflection,interfaces, standing waves, refraction, and differences in tissuethermal conduction or blood flow. It is estimated that at an output 1W/cm2 there is a rise of 0.8 C/min if vascular cooling effects areignored.

Alternatively, instead of the transducer head 16 being moved by theclinician over the tissue of the eyelid 24, the transducer head 16 maybe stationary or fixed to the eyelid 24. If mobile, a ultrasoundtransducers could be employed and this may have a single active elementthat both generates and receives high frequency sound waves, or twopaired elements one for transmitting and one for receiving. In contrast,if stationary, a head 16 with multiple components could vary theultrasound beam applied from the transducer.

The transducer head 16 may have moving components within the head thatvary the ultrasound beam applied from the transducer 16.

A phased array may be used to vary the application of the ultrasoundacross the treatment field. This may allow the clinician to simply applythe transducer 16 (or probe attached thereto) to the eyelid 24 orfasten/adhere it in place without constantly moving the transducer 16(or probe attached thereto). With this phased array the risk of having astanding wave or a hotspot may be greatly reduced. The phased arraycould be arranged in a strip (linear array), a ring (annular array), acircular matrix (circular array), or a more complex shape such as anellipse that would conform to the shape of the eyelids.

The system 10 may also include a display for displaying images and videofrom ultrasound machine 12 and a computing system 32 with a processorand memory 34 for processing captured data, images and video. Thecomputing system 32 may be operable to store data/images/video in memory34 and/or an imaging database 36. The transducer 16 may have an imagingcomponent 28. The ultrasound 12 and transducer 16 may be used in adiagnostic setting to image the gland and eyelid 24, as well as atherapeutic setting to heat the eyelid 24 and gland. The gland andsurrounding tissues could be imaged in real time as the treatment isprovided by the transducer head 16. A dual transducer may be used toimage and treat. The images may provide a visual indication of treatmentprogression for a patient.

The imaging camera could visualize the consolidated meibum in themeibomian gland and its ductules. It could also quantify the amount ofmeibum in the glands. A reduction in meibomian gland volume wouldconfirm that oil was expressed out of the glands and ductules.

Referring now to FIG. 2 there is shown a diagram of a meibomian glandand duct 40, with a fat blockage 44. There is also shown an illustrativeview of the meibomian gland and duct 40. As shown the meibomian glandand duct 40 may be located in the eyelid 24 near the eye globe 42.

Ultrasound energy may be passed into the ocular tissues, which mayincite inflammation and potentially cause cataract formation. Inaccordance with embodiments described herein, systems, methods and usesmay involve a vaulted scleral contact lens 22. The lens 22 may be placedover the eye globe and under the eyelids 24 to form a chamber of air.The chamber of air may be between lens layers or the posterior surfaceof the contact lens and the cornea itself. Since ultrasound energy doesnot pass well through gases this vaulted chamber may act as a barrier toultrasound transmission effectively shielding the eye from theultrasound energy. Alternatively, a lens speculum may be applied to theeye to elevate eyelid 24 from eye globe and create an airspace betweeneye globe and eyelid 24.

The transducer 16 may be applied to eyelid at different angles anddirections. Referring now to FIG. 3 there is shown uses of therapeuticultrasound for eye conditions. In one example, a transducer head 16 mayhave a curved shape to complement the eyelid 24. The transducer head 16may propagate ultrasound waves towards the eyelid 24 and eye globe 42 toliquefy fat blockage 44 in the gland 40. A lens 22 may create or includea chamber of air 46 to protect the eye globe 42. The lens 22 may beplaced over the eye globe 42 and under the eyelids 24 to form a chamberof air 46 between the posterior surface of the contact lens 22 and thecornea itself. The chamber of air may also be within the lens, betweenlayers of the lens.

The contact lens could also be made of an absorptive material that doesnot allow penetration of ultrasound energy, or the chamber of air (e.g.air gap) may block penetration of ultrasound energy. In some cases thecontact lens may form a sufficient barrier so that it would not need tobe vaulted off the globe. Alternatively, a lens speculum (not shown) maybe applied to the eye to elevate eyelid 24 from eye globe 42 and createan airspace between eye globe and eyelid 24. In another example, thetransducer head 16 may propagate ultrasound waves away from the eyeglobe 42 using thin plates which form part of transducer head 16.

Referring now to FIG. 5 there is shown another diagram of a use oftherapeutic ultrasound for eye conditions. The transducer head 16 mayhave a curved shape to complement the eyelid 24. The transducer head 16may propagate ultrasound waves towards the eyelid 24 and eye globe 42. Alens 22 may be positioned on top of the cornea and covered by the eyelid24. The lens 22 may be vaulted to protect eye globe 42 by creating achamber of air between the posterior surface of the contact lens 22 andthe cornea itself. The lens 22 may also include multiple layers creatinga chamber of air. The contact lens 22 may also be made of an absorptivematerial that does not allow penetration of ultrasound energy. In thiscase the contact lens would form a sufficient barrier so that it wouldnot need to be vaulted off the globe. Coupling gel 23 may be applied ontop of the eyelid 24 to act as a coupling medium between the tissue andthe transducer 16. Ultrasound waves may be transmitted by the transducer16 into the eyelid 24.

A temperature and attenuation measurement device may be positionedproximate to the lens or other area to collect and record temperaturesand attenuation measurements to monitor heating of eye 42. For example,a measurement tool 25 may be positioned on the lens 22 in order to taketemperature measurements. The measurement tool 25 may be a thermocouple.The measurement tool 25 may provide temperature data to controller. Ifthe temperature exceeds a safety threshold the controller mayautomatically shut off the transducer 16 to ensure the eye 42 is notdamaged, automatically adjust the treatment parameters to reduce thetemperature, or send an alert notification. The measurement tool 25 maybe positioned on the lens 22 using glue or other adhesive. It may alsobe built within the lens 22.

Referring now to FIG. 4 there is shown a method 100 of using highfrequency ultrasound for eye conditions. The method 100 may be use highfrequency ultrasound to liquefy solidified fats in the meibomian gland,or other glands/ducts. At 102, a clinician may administer a drop oftetracaine or equivalent topical anesthetic unto the eye. At 104, a lens22 may be placed onto the eye. At 106, the ultrasound transducer 16propagates the high frequency ultrasound waves (such as 0.2 to 50 MHz).The ultrasound transducer 16 may be affixed on or within the lens 22.The ultrasound transducer 16 may also be applied to both closed eyelids24 through a coupling gel 20 medium for a treatment period, such as forexample a two to five minutes treatment for each eye, or for longerdepending on the frequency. After the heating treatment, at 108, amechanical roller may be used to express oil secretions from themeibomian glands. This may occur while the contact lens 22 shield isstill in place. For example, this roller may be applied from a proximalto distal direction in the direction of the meibum flow within theglands themselves. Alternatively, a cotton swap (e.g. Q-tip) or otherinstrument may be used to guide oil. Post treatment, the patient may beplaced on a short course of topical steroids (or NSAIDs) to minimize anypost-procedural inflammation.

Referring now to FIG. 6, there is shown a diagram of a use oftherapeutic ultrasound with an attachment for eye conditions accordingto some embodiments. The attachment 52 may couple to the transducer 16in order to propagate ultrasound waves to the eyelid 24. The attachment52 may include a protective portion 50 shaped to complement the eye 42and protect the eye 42 from the ultrasound waves. The attachment 52 andprotective portion 50 may clip onto the patient's head or eye 42 (orotherwise attach) for the duration of the treatment period. Embodimentsmay include an external transducer shaped to complement the gland fortreatment. The transducer may be of a longer length than the air gaplens to maximize treatment area. The external transducer may also beable to move along the entire length of the meibomian glands.

Referring now to FIG. 7, there is shown another diagram of a use oftherapeutic ultrasound with an attachment for eye conditions accordingto some embodiments. The attachment 56 may couple to the transducer 16in order to propagate ultrasound waves through the eyelid 24 but awayfrom eye globe 42. The attachment 56 is shaped to complement the eye 42and eye lid 24 and position there between. In this example, theultrasound waves propagate away from the eye 42 to reduce chance of harmdue to heat. This may protect the eye 42 from the ultrasound waves. Theattachment 56 may clip onto the patient's head or eye 42 (or otherwiseattach) for the duration of the treatment period. This is anotherexample of an external transducer which may be used with the air gaplens.

As described herein, ultrasound energy may be passed into the oculartissues, which may harm the eye. In accordance with embodimentsdescribed herein, systems, methods and uses may involve a contact lens22. The lens 22 may include a chamber of air created by lens layers. Thelens 22 may be placed over the eye globe and under the eyelids 24. thelens 22 may form or provide a chamber of air to protect the cornea. Thechamber of air may act as a barrier to ultrasound transmissioneffectively shielding the eye from the ultrasound energy. Alternatively,a lens speculum may be applied to the eye to elevate eyelid 24 from eyeglobe and create an airspace between eye globe and eyelid 24.

Dry eye is a complex disorder that affects a significant portion of thepopulation. A form of the disease is Evaporative dry eye disease whichis a disorder of the ocular surface and tear film causing pain and lowvision in a significant portion of the adult population. The most commoncause is obstructive meibomian gland dysfunction (“MGD”), whereby themeibomian glands secrete abnormally keratinized, viscous meibum with amelting point approximately 3-4° C. higher than normal. Dry Eye istypically treated with heat, aiming to liquify the solidified meibum atthe meibomian ducts. The ocular surface is coated by a tear/lipidbilayer. The lipid functions to provide a smooth optical surface, andretard tear evaporation. Dry eye may be caused by obstructed meibomianglands. Reduced meibum may lead to increased and excessive tearevaporation.

Embodiments described herein may reduce or treat dry eye using anultrasound hyperthermia device with a contact lens. There may be aninternal transducer contained within a contact lens with an internal airgap. The internal transducer may be of polyvinylidene fluoride (PVDF)film (or other material) for example. This is an example transducer andother types may be used. For example, piezoelectric transducer may beconstructed from a piezeoelectric ceramic with perovskite structure,such as lead zirconate titanate (PZT) its varieties. The transducer mayalso be made from a piezoelectric polymer, such as PVDF. Piezoceramicsmay include PZT and PZT-varieties, barium titanate, lead titanate, leadzirconate titanate, potassium niobate, lithium niobate, lithiumtantalate, sodium tungstate, zinc oxide, and so on.

A prototype of this device may be built in a planar geometry to test itsfeasibility. Ex vivo experiments with porcine eyelid and cornea tissuemay be performed with the device with low amplitudes (30-35 V) and arelatively low duty cycle (25%) as an illustrative example. Atemperature rise of 4.5° C. in the eyelid may be achievable in a shorttimeframe. A vacuum mould may be used to form a spheroidal concavity ina PVDF film. This film may then be fixed between two contact lenses(created an air gap) providing an air backing to the transducer, withthe electrical connections contained inside this gap.

Dry eye is a complex, multifactorial disorder of the ocular surface andtear film due either to tear deficiency or excessive tear evaporation.It affects vision and comfort in a significant portion of the population

The meibomian glands are modified sebaceous glands diffusely locatedwithin the inner tarsal plate, numbering approximately 25 and 20 in theupper and lower lids, respectively. They are responsible for thesecretion of meibum, the lipid portion of the tear layer that servesseveral purposes. Primarily the meibomian lipid is a hydrophobic seal onthe aqueous tear film, preventing its evaporation and enhancing the filmstability through a reduced surface tension. Like Dry Eye, MGD is abroad collection of different conditions with many causes. However, themost common clinical form of MGD is obstructive, diagnosed according toreduced excretion or abnormality of the meibum. The common case findsobstructive MGD, where the ducts by which meibum reaches themuco-aqueous surface are blocked by abnormally viscous, keratinizedmeibum. Ultimately, MGD entails that insufficient levels of meibomianlipid are present for sealing the aqueous tear film.

A method of treatment for evaporative dry eye caused by MGD has beenheat therapy in the form of warm compresses and/or manual glandexpression through mechanical pressure. Meibomian lipid is liquid at lidtemperature in healthy patients, melting at 32-40° C., however abnormalmeibum has an elevated secretion temperature by approximately 3° C.Studies of the chemical composition of meibum have found an increase inphase transition temperature of 4° C., defined by several parameters ofinter-molecular order. Hence, heat therapy aims to liquify thekeratinized meibum at the meibomian ducts by raising the temperature ofthe tarsal plate. Careful application of heat to the eyelids mayincrease the thickness of the tear lipid layer. Treatment methods thatuse heat sources may apply heat to the outer surface of the eye, whereefficacy of heat applied to the outer surface of the eyelid is debatablesince the applied heat must diffuse through the dense muscle tissue ofthe tarsal plate with a strong vascular supply. This may be an evengreater impediment for patients attempting to self-administer warmcompresses since care must be taken to ensure the compresses remain at aconstant, elevated temperature to provide an effective heat source.

Embodiments described herein may use High Focused Intensity Ultrasound(HIFU). HIFU may be applied with relatively low duty cycles (≦10%),which allows the tissue to cool and achieve a stable temperatureincrease within the 39-44° C. regime. Increasing the duty cycle whileconcomitantly decreasing the amplitude results in comparable powerdeposition to HIFU, but with a lower ultrasonic intensity. Given themelting temperature of keratinized meibum at ˜42° C., this range may beused for a mild ultrasound hyperthermia treatment.

Embodiments described herein may an ultrasound device for mildhyperthermia in the tarsal plate. Embodiments described herein mayelevate the temperature of the eyelid interior to the melting point ofabnormal meibomian lipid, taken as 41-43° C.—a regime demonstratedeffective. Due to the strong vascular supply of the tarsal plate, theinterior of the eyelid may be assumed to be near the temperature ofblood, at around 37° C.

Embodiments described herein may use a device that consists of atransducer within a large scleral contact lens with an air gap, whereinthe transducer is attached to the lens (affixed thereto or within),which is in contact with the conjunctival epithelium. Inside the air gaplens, the transducer is air-backed and hence reflects essentially allacoustic energy forwards through the front lens into the tarsal plate.This is a safety consideration, as the application of heat could causecorneal deformation, possibly affecting or impairing vision. As low atemperature rise in the cornea as reasonably possible may be desired,such as below the 50° C. upper bound. An extremely conservative limit of<40° may be used, corresponding to a maximum 6° C. rise given the ocularsurface temperatures measurements in the range 32-34° C. have beenreported. Thus the ultrasonic energy propagates outwards towards thetarsus, delivering heat directly to the Meibomian glands. The acousticimpedance mismatch of the transducer and air reacts essentially allpressure waves away from the cornea, which is an important safetyconsideration discussed. The device may include a high frequencylead-zirconium titanate (e.g. PZT) piezoceramic transducer in someembodiments.

To demonstrate feasibility as a treatment device, a prototype may beconstructed with a flat geometry with contact lens material and a 21 MHzPVDF film. This example illustrative geometry was elected to mimic thedesired lens configuration while simplifying construction. In addition,a theoretical model of heat delivery due to acoustic pressure waves maybe developed for this simplified geometry and compared with theexperimental results.

Heating the external eyelid surface may require sufficient heattemperatures to diffuse through the strong eyelid vasculature.Temperature rise in the cornea may cause deformation. When heating theexternal surface of the eye, the temperature of the outer eyelid ishigher than the temperature of the inner eyelid. That is, a lineardecrease may be proportional to depth. Equilibrium may be establishedover time.

Treatment devices and systems in accordance with embodiments describedherein may heat tarsal plate to 41° C. to 43° C. Treatment devices andsystems in accordance with embodiments described herein may not depositultrasonic energy into cornea. Treatment devices and systems inaccordance with embodiments described herein may keep cornea under 40°C. Treatment devices and systems in accordance with embodimentsdescribed herein may obtain a reasonable change in temperature for atreatment timespan. These are illustrative examples.

Embodiments described herein may involve use of a contact lens toprotect an eye during treatment of the eye with a ultrasound device. Asdescribed herein, there may also be a measurement tool 25 which may be athermocouple. As a safety mechanism a thermocouple could be placed ineither the front side, back side, or both sides of the contact lens.This thermocouple may trigger the ultrasound device to turn off if thetemperature was raised to an unsafe level (e.g. 48 degrees celsius).This thermocouple may also give real time active feedback of temperaturethus giving the technician/doctor the ability to modulate the ultrasoundsettings to achieve a safe and effective hyperthermia. The modulationand adjustments may be automatically configured as well. The degree ofhyperthermia could also be measured and thus modulated by other meanssuch as infrared.

Referring now to FIG. 8 there is shown an example embodiment that mayinvolve a contact lens 70 a, 70 b to protect the eye. The contact lens70 a, 70 b includes an inner lens 70 b and an outer lens 70 a and spacedapart to create an air gap 72 (e.g. chamber of air). The inner lens 70 band outer lens 70 a may be attached at ends. The inner lens 70 b may bepositioned to protect the cornea 80. The inner lens 70 b and outer lens70 a may be positioned under the eyelids 78. The contact lens 70 a, 70 bprotects the eye during application of ultrasound energy by transducer74 and coupling 76 via the air gap 72 which may reflect acoustic energy.This configuration and implementation may provide efficient manufactureand use. In this example, an external PZT transducer 74 may be placed ontop of the eyelid. The contact lens 70 a, 70 b with the internal air gap72 may be placed on cornea 80. The external PZT transducer 74 maydeposit ultrasonic heating onto eyelid 78 surface where the heat maydiffuse inwards.

A design is proposed in which a high frequency piezo film transducer ismounted within a contact lens. A high frequency may be desired since theattenuation of an acoustic wave increases proportionally to frequency,with a corresponding greater heat deposition. The lens contains aninterior air gap between its inner surface mounting the sclera and outersurface contacting the tarsal conjunctiva. These surfaces may bereferred to as scleral and tarsal, respectively. The transducer may bemechanically attached (or otherwise coupled) to the interior of thetarsal surface, moulded to the concavity of the lens. Its active facemay be directed outwards towards the tarsal plate. The air gap providesan air backing layer to the transducer, reflecting essentially all ofthe acoustic energy forwards due to the impedance mismatch of thepiezoelectric material and of air. This is to ensure that no pressurewave propagates through the scleral surface into the cornea, causingunwanted heating in the eye. Furthermore, the air gap acts as aninsulating layer, delaying the heat diffusion through the front lens andeyelid into the cornea. When mounted onto the sclera, the eyelids wouldclose overtop the lens, holding the device in place during thehyperthermia treatment. The electrical connections are contained withinthe air gap, with wiring exiting the lens through a hole sized to thewires and sealed airtight, passing through the palpebral fissure.

A schematic of the design when placed atop an eye is shown in FIG. 9.The example embodiment may involve a contact lens 70 a, 70 b to protectthe eye. In this example, heat from conjunctival surface within air gap72 between the outer lens 70 a and inner lens 70 b may be used. Aninternal transducer 82 coupled to a RF signal cable 84 may be positionedwithin air gap 72 between the outer lens 70 a and inner lens 70 b. Inthis example, heat is applied directed to the tarsal plate, which mayprotect the outer surface of the eyelid. The air gap 72 may protect thecornea 80. The internal transducer 82 may be air-backed and mounted ontothe inside of the air gap lens 70 a, 70 b, 72. Ultrasonic heating energyis deposited directly on tarsal surface.

The feasibility of the internal air gap for protecting the cornea duringan ultrasound hyperthermia treatment in the eyelid may be demonstratedusing an external high frequency transducer with a protective contactlens. With this established, a prototype of the device with a planargeometry may be constructed, and a mild hyperthermia experiment may beconducted to monitor the temperature increase in eyelid and corneatissue. In addition, a simplified 1-dimensional model of heatpropagation with ultrasound sources may be created in MAT-LAB to modelthe heating of the prototype's elements using a finite element analysis,for example.

Referring now to FIG. 10 there is shown an example experiment system 90including a transducer 74 and a contact lens 70 a, 70 b with air gap 72in accordance with the configuration shown in FIG. 8. A thermocouple 86a, 86 b may be coupled to the outer lens 70 a and inner lens 70 b tomonitor temperatures.

A hyperthermia experiment may be performed in the configuration seen inFIG. 10. Two thermocouples may be embedded within lens. A protectivecontact lens with an internal air gap may be built from two contactlenses with suitable radii of curvature to allow a gap (e.g. 2 mm) atthe epicenter when the larger was fit overtop the smaller. This may beplaced atop the cornea. The eyelid tissue may be laid overtop this lens.A transducer (e.g. 15 MHz) may be positioned overtop the eyelid,applying a firm downward pressure and coupled with ultrasound gel. A 25%duty cycle sinusoidal RF signal may be used as a signal source with apeak to peak voltage of 40 V. The temperatures of both the eyelid andthe cornea may be monitored during several minutes of treatment untilthe eyelid had increased by 4.5° to determine the efficacy of theprotective air gap.

FIG. 11 provides a illustrative example planar prototype that may beconstructed with 21 MHz PVDF and fluorosilicone acrylate sheets (FSA).The planar prototype may have a illustrative simpler geometry with a 250μm lens layer, a 2.65 mm air gap, and another 250 μm lens layer. Theseare illustrative examples and variations in materials and configurationsmay be used for various embodiments.

A plastic frame may be milled with a cylindrical through-hole. Flatcylindrical disks of FSA of thickness 250 μm may be precision cut andused as lens-mimicking material for the prototype. FSA is a materialused for larger corneal lenses with sufficient concavity to house atransducer, complete with its electrical wiring. The thickness of 250 μmwas chosen as an example of contact lenses. Copper leads were epoxied tothe electrodes of a 52 μm, 1 cm2 PVDF piezoelectric film with acorresponding centre frequency of 21 MHz using silver conductive epoxy.The transducer may then be epoxied with non-conductive epoxy to thecentre of an FSA lens. The FSA lenses may then be both fixed to theplastic frame with epoxy. The copper leads may be cut from flex circuitpaper, and may not significantly displace the FSA layer from the plasticframe when protruding from it. The leads may then be soldered to acoaxial cable with an SMA adapter.

An eyelid may be coupled to the upper FSA lens overtop the transducerwith ultrasound gel. The cornea may be in contact with the bottom lens,again coupled with ultrasound gel. More ultrasound gel may be applied tocouple the cornea both thermally and acoustically to the lens, which,due to its planar geometry (for the prototype), may not flatly abut thespheroidal cornea. Two sheathed thermocouples may be embedded in thelens, and aligned such that they were directly underneath and overtopthe transducer, respectively. A 25% duty cycle sinusoidal pulse ofduration 80 μs may be amplified by 60 dB for source peak to peak sourcevoltages to the transducer of 50, 60, and 70 V in three separate trials.In each trial, the source may be applied for several minutes until thecharacteristic drop in the heating curve of the eyelid is observed inthe range of 3-5° C. temperature increase.

Referring now to FIG. 12 there is shown an example experiment system 92including an internal transducer 82 within a contact lens 70 a, 70 b andair gap 72, in accordance with the configuration shown in FIG. 9. Athermocouple 88 a, 88 b may be coupled to the outer lens 70 a and innerlens 70 b to monitor temperatures.

A 1 dimensional finite element model may be used for the exampleexperiment system 92, created using a series of layer objects, eachrepresenting the physical media in a vertical cross-section in thehyperthermia. The use of a single dimension considers the temperaturerise to a constant with respect to horizontal heat diffusion, howeverconvective losses at the sides of each layer were considered to moreaccurately simulate the temperature profiles. A presentation of themodel is to follow.

The cornea and eyelid may be treated as tissues with distinctproperties, and the ultrasound gel between these and the lenses may betreated as water. The approximate dimensions and order of the layers,moving vertically downwards, is given below in table 1.

To determine the thicknesses, the solid layers of the eyelid tissue, thelenses, and the separation between the two lenses may be measured. Thefluid layers were reasonably approximated by the separation between thetissue once force may be applied to the tissues to hold them flush tothe lens. The cornea may be assumed to be indistinguishable from theaqueous humour. The corneal dimensions may be the entire diameter of theeye (˜2 cm for an experiment).

TABLE 1 Order and thicknesses of the media used in the simulation.Position Media Thickness (mm) 1 Eyelid Tissue 0.5 2 Water 1 3 FSA 0.2504 Air 2.65 5 FSA 0.250 6 Water 1 7 Cornea/Eye 20

The physical properties of each medium such as density and celerity maybe measured, where possible, and otherwise obtained from other sources.The acoustic attenuation of both fluorosilicone acrylate and eyelidtissue may be measured by comparison of pulse-echo signal levels fromshort pulses directed towards a reflecting quartz plate with a 15 MHzPZT imaging transducer, through degassed water and then through therespective materials. The attenuation of both as a function of frequencyis shown for reference in FIGS. 20 and 21. The density of FSA may becomputed from the mass of a cylindrical block of the material of knowndimensions, and its celerity may be calculated from the same pulse-echoexperiments as the attenuation.

The imaging camera could visualize the consolidated meibum in themeibomian gland and its ductules. It could also quantify the amount ofmeibum in the glands. A reduction in meibomian gland volume wouldconfirm that oil was expressed out of the glands and ductules.

Eyelid tissue is comprised of several layers. The outermost layer ofskin is the thinnest in the body at less than 2 mm due to littledevelopment of the dermis; as such it is primarily composed of muscleand fibrous membranes. As such, the eyelid may be treated as muscle, notskin, when selecting its physical and thermal properties from theliterature. The physical properties of each layer, where applicable, aresummarized in table 2 where ρ denotes the density; c_(—)0, the speed ofsound; and α, the attenuation.

TABLE 2 Physical properties used in the simulation. An asterisk denotesa measured quantity. p (kg/m³) c₀ (m/s) α (dB/cm) Eyelid 1050 1580 288 FSA  1266*  1490*  86* Cornea 1062 — — Water 1000 1500  0 Air     1.225 350 —

The thermal properties of each media are summarized in table 3. Here, kdenotes the conductivity and c, the specific heat capacity. For FSA, thethermal properties of polymethylmethacrylate (PMMA) may be used in lieu,as PMMA may be used as material in contact lenses.

TABLE 3 Thermal properties used in the simulation. c (J/kg/K) k (W/m/K)Eyelid 3600 0.55 FSA 1466 0.167 Cornea 3740 0.58 Water 4182 0.6 Air 10000.025

To determine the temperature profile T(x,t) in each layer as a functionof depth (x) and time (t), the heat equation may be numerically solvedin each layer using discrete elements at specified depths according to:

$\begin{matrix}{\frac{\partial{T\left( {x,t} \right)}}{\partial t} = {{\gamma \frac{\partial^{2}{T\left( {x,t} \right)}}{\partial x^{2}}} + \frac{\overset{.}{Q}\left( {x,t} \right)}{pc}}} & (1)\end{matrix}$

$\gamma = \frac{k}{pc}$

where is the thermal diffusivity in m²/s and {dot over (Q)} representsan ultrasonic heat source term per unit volume, which, for an incidentacoustic intensity I₀, is expressed using the time-averaged intensityas:

{dot over (Q)}(x)=αI ₀ e ^(−αx)  (2)

where x is the depth the pressure wave has travelled in the medium.

I₀ may be computed based on a rudimentary power dissipation model of aparallel plate capacitor with capacitance C and known area A. Anefficiency ε of conversion from electrical to mechanical energy may beassumed, and a PiezoCAD simulation may compute the upper bound for theenergy conversion to be 20%. As this is very high estimate, anefficiency of ten times less at 2% may be assumed, as there areresistive losses associated with conductive epoxy. Using the poweramplitude of a capacitor, for an input voltage V₀ at frequency f, theacoustic intensity is:

$\begin{matrix}{I_{0} = {\varepsilon \frac{2\pi \; f\; {CV}_{0}^{2}}{A}}} & (3)\end{matrix}$

The ultrasonic wave at the surface of the capacitor may be considered auniform plane wave in one dimension. No acoustic energy may be assumedto propagate through the air medium; instead the energy may be reflectedand the incident intensity in the FSA layer 3 was doubled accordingly. Afurther consideration may be given to the thin layer of epoxy that heldthe transducer to the lens surface by subtracting a known attenuation ofa common epoxy.

The boundary conditions between each layer may be specified according toconvective heat transfer at that boundary. The spatial derivative of theith layer

$\frac{\partial T_{i}}{\partial x}$

may satisfy

$\begin{matrix}{{{- k}\frac{\partial T_{i}}{\partial x}} = {h\left( {T_{i + 1} - T_{i}} \right.}} & (4)\end{matrix}$

where T_(i) and T₁₊₁ are the temperatures on either side of the boundarybetween two layers. The constant h is a heat transfer coefficient inW/m²K. Although h is dependent entirely on the interface type anddifficult to accurately measure, representative ranges arereadily-available for static air and water, as 10-100 and 20-1000 W/m²,respectively.

To account for convective losses along the horizontal faces of eachmedia layer in the hyperthermia experiment, an additional boundary maybe considered for each layer. The tissues used in the experiment may bestored in saline and hence may be covered in an aqueous layer. Becauseof this, the value of h in equation 4 may be identical to that forconvective transfer with the water layers. Hence, as an approximation,the derivative

$\frac{\partial T_{i}}{\partial x}$

as computed through equation 4 may be considered an additional heat lossterm in equation 1.

FIG. 13 illustrates an example thermal model. FIG. 14 illustrates anexample acoustic source model showing time averaged intensity againsteyelid, water, FSA, and air.

The experiments with an air gap lens may show that the air gap lens maybe a good protective measure. As shown in FIG. 15, the eyelid tissue maybe heated with the characteristic shark fin profile. The heating in thecornea may occur after a short delay and may not reach its peaktemperature until after 3 minutes of treatment time, despite thetransducer source having been extinguished at 2.5 minutes.

FIG. 15 illustrates a chart of temperature rise against time for theexternal transducer 74 configuration. For an example experimentsimulation, a 4.5° C. rise in temperature was shown in less than threeminutes. For the example experiment simulation, no ultrasound energypenetration was shown through air gap 72. There may be a small heatdiffusion into cornea, such as 0.5° C. Low power may be used for heatingwith a PZT transducer 74.

FIG. 15 demonstrates the safety of an air gap lens for ultrasoundtreatment in the cornea. The heating profiles of the eyelid and corneaare distinctly different; instead of the sudden ramp-up due to anapplied heat source, the cornea gradually begins to warm up due todiffusion through the lens. There is a thermal propagation delay ofseveral seconds in between the temperature rise of the red eyelid curveand the blue corneal curve that illustrates this. In addition, the peaktemperature attained by the cornea occurs after the ultrasound sourcehad been turned off, indicating that the cause of its heating wasdiffusion of the heat deposited in the eyelid.

FIG. 16 illustrates a contact lens area proximate to FSA and ultrasoundgel. FIG. 17 illustrates a chart of temperature rise against time forFSA.

Heat diffusion through the air gap of the lens may be relativelyminimal. See for example, the air gap given the chart in FIG. 15 showingthat no ultrasound may be propagated through to the inner lens. In someinstances, a temperature rise in the cornea may be 0.5° C., which iswithin even the conservative safety limits of 6° C.

For source amplitudes of 30 and 35 V, temperature rises of 4.5° may beobserved in the eyelid, suitable to raise the inner tarsal plate frombody temperature to the desired melting point of abnormal meibum.Naturally, the larger source amplitude produced this target temperaturerise faster; hence the amplitude or duty cycle of the source may bemodified in the future to obtain the temperature rise in a desirabletime limit—preferably one that minimizes the corneal temperature risedue to diffusion.

FIG. 18 illustrates example vacuum molded PVDF to construct sub-tarsaldevices. The transducer may be shaped to complement the eye surface. Thetransducer may be secured to lens and then electronics may be enclosedwith air backing.

To produce a piezo film that will fit well into the tarsal surface, avacuum mould may be a viable method to shape the film. Depicted in FIG.18( a)-(e) with the PVDF film shown, and the vacuum mould (made fromporous metal or plastic) shown with black circles. First a PVDF layerwith deposited electrodes may be mounted overtop a vacuum-forming mouldwith a cavity (a), and a vacuum may be applied to the layer to mould it,forming the PVDF to the desired shape (b). Next, with the vacuum stillapplied, a lead may be epoxied to the concave side of the layer withconductive epoxy (c). After curing, the concave PVDF may be filled withnon-conductive epoxy (brown) for structural strength (d). The film maybe then removed, the excess material may be cut from its outer radius,and the second lead may be epoxied to the convex side of the film withconductive epoxy (e). This transducer may be mounted to the inner faceof a contact lens. The electrical connections may be soldered, and thenenclosed inside an air gap (f).

FIG. 19 illustrates example prototypes for PZT internal transducers forembedding within air gap contact lens. PZT has a high-electrical toacoustic energy transfer on transmission. Epoxy and FSA may attenuate ataround 8 dB/mm. The thickness may be minimized. Two example PZTprototypes are shown for illustrative purposes, with differentattenuations due to epoxy and the lens. One example includes a smalltransducer with minimal epoxy fitted inside a lens. Another exampleincludes a larger transducer epoxied to the lens with its tip removed.The larger the transducer the more difficult it may be to ensure an airgap between the inner and outer lens. The prototypes may be used to heatthe tarsal plate by 5° C. for example. An air gap may be integral tolens design.

Embodiments described herein may use an ultrasound hyperthermia devicecontained within a contact lens with an internal air gap. Thepiezoelectric film may produce an acoustic wave to warm the tarsalplate, targeting the meibomian glands, and is also air-backed in orderto avoid the propagation of ultrasonic energy backwards into the cornea.A prototype of this device may be built with contact lens materials in aplanar geometry to test its feasibility. Ex vivo experiments withporcine eyelid and cornea tissue may be performed with the device withlow amplitudes (30-35V) and a relatively low duty cycle (25%).

A temperature rise of 4.5° C. in the eyelid may be achievable in a shorttimeframe.

A vacuum mould may be used to form a spheroidal concavity in a PVDFlayer. This film may then be fixed between two commercial contact lenseswith an air gap providing an air backing to the transducer, with theelectrical connections inside this gap. Such a device may be suitablefor in vivo preclinical experiments.

To measure the attenuation of FSA and porcine eyelid (which may be usedfor experiments), samples of known thickness may be placed atop a quartzplate, and the resulting pulse-echo signal may be compared with thesignal from the quartz plate without any obstruction. In both cases, thetransmission coefficients for the sample, quartz, and water may beaccounted for. Since a broad band transducer may be used, the frequencyspectra of the signals may be used for comparison, rather than thesignals themselves in the time domain. For the frequency rangeconsidered, FIGS. 22 and 23 show the attenuation coefficients forporcine eyelid and FSA, respectively.

Embodiments described herein relate to an ultrasonic device for mildclinical hyperthermia of the tarsus is proposed. The design consists ofa piezoelectric transducer mounted within a specialized contact lens. Anexample configuration is shown in FIG. 9.

FIG. 22 illustrates another example of an air gap lens according to someembodiments. The air gap lens has lens layers, including a tarsal face202 and a corneal face 204, that define an air gap 206 or a chamber ofair. In this example a transducer 208 is located within the air gap 206and not in contact with the lens layers. The transducer 208 is coupledto a cable 210 to supply energy for delivering ultrasound. Thedimensions noted are illustrative examples only.

The closed air chamber within the lens structure may ensure that thereis a built-in air barrier to ultrasound which will provide sufficientacoustic impedance. With such a design ultrasound contact gel can beused on the surface of the eyelid or periocular tissue without concernof the gel or any other fluid getting into the air barrier. Asultrasound does not propagate well through gases this design wouldprovide high acoustic impedance and thus shield the eye from ultrasoundenergy. The different layers of the lens may also comprise an absorptivematerial to block penetration of ocular tissue by the ultrasound waves.In particular, if the ultrasound is being applied externally through aseparate ultrasound probe, then outer surface of the contact lens whichabuts the tarsal conjunctiva of the eyelid could be made of anabsorptive material or have an absorptive coating hat would uniformlyheat and further act to warm the inner eyelid and the meibomian glands.

The air gap lens contains an internal air gap 206 between its inner facemounting the sclera and cornea, and outer face beneath the tarsalconjunctiva. These inner and outer faces are referred to as a tarsalface 202 and a corneal face 204, respectively. The air gap 206 isensured by fabricating a lens that steeply vaults the cornea at thelimbus with several millimetres of clearance, and subsequently securinga second lens that does protrude as steeply from the sclera to theposterior of the first, such that the clearance results in the air gap206. The vaulting curvature of a lens may be a large-diameter scleralcontact lens for patients with abnormally sized corneas, or may be acustomized lens. The lens may be fabricated to have different curvaturesalong the length of the eye, such that the lens abuts the sclera andprotrudes outwards at the corneal limbus, vaulting over the cornea andprotruding from the base.

The transducer 208 may be mechanically secured to the posterior tarsalface via an epoxy, but may not contact the tarsal lens 202 face. Assuch, the transducer 208 may be contained inside the air gap 206 withthe active face directed outwards towards the tarsus. The aig gapprovides an air backing to the transducer 208, such that the acousticimpedance mismatch of the transducer 208 material and the air may ensurethe acoustic waves do not propagate towards the eye.

Accordingly, an ultrasonic hyperthermia device for the tarsus mayinclude an air gap lens. The air gap 206 within the lens reflectsultrasonic energy towards the tarsal plate, shielding the cornea.

When the lens is placed overtop the sclera, the eyelids may hold thedevice in place through the mechanical pressure of the orbicularis. Theuse of a scleral contact lens may also ensure the axial alignment of thetransducer 208 with respect to the visual axis of the cornea duringtreatment. The electrical connections to the active and groundelectrodes of the transducer 208 are connected via sub-millimeterdiameter coaxial cable, which exits the lens via a milled through-holethat is fitted to the cable 210 diameter and sealed airtight. The cable10 may exits the eyelids from the palpebral fissure, near the lateralcanthus.

During treatment, a continuous wave excitation voltage may be appliedacross the transducer 208 terminals with a low duty cycle (less than tenpercent for example). The acoustic waves may be directed towards thetarsus from the transducer's 208 active face, and reflected away fromthe cornea by the air backing. The forward-propagating ultrasound may beattenuated by the eyelid tissue, thus depositing thermal energy in thetarsus. Power may be applied to the transducer continuously for atreatment period of 10-15 minutes, as an illustrative example. Duringthis time, the basal temperature of the eyelid may be brought toequilibrium at the elevated target treatment temperature of 41-43degrees Celsius. During steady state conditions, this temperature maynot fluctuate, and the constant elevated temperature liquefies the lipidwithin the meibomian ducts, allowing it to flow and coat the tear film.After this time, the power may be ceased, allowing the eyelid to returnto its base temperature.

FIG. 23 illustrates a schematic showing the placement of the lens 212and transducer 214 underneath the eyelids, with the wiring 216 exitingthrough the palpebral fissure near the lateral canthus. FIGS. 24 and 25illustrate further example schematics of the air gap lens.

Table 4 provides details on the marginal eyelid composition in orderfrom the anterior to the posterior surfaces.

TABLE 4 Order Layer Thickness (mm) Tissue 1 Dermis 0.05 Dermal 2Epidermis 0.3 Epidermal 3 Orbicularis 0.15-0.65 Muscle 4 Tarsal Plate  1-1.5 Fibrous 5 Conjunctiva Mucous

Ultrasound hyperthermia may deliver heat to tissue via the absorption ofacoustic waves. For a medium with an acoustic attenuation α, the meanheat deposition rate {dot over (Q)}_(a) at a distance z from the sourcetransducer is:

{dot over (Q)}_(a)=2α I exp{−αz}  (5)

where Ī is the time-averaged ultrasonic intensity at z²⁰. Equation 5shows the exponential decay of the field intensity with axial distancedependent on α.

The attenuation is frequency-dependent, increasing monotonically withfrequency as:

α(f)=α₀ f ^(n)  (6)

where the constants α₀ and n are tissue properties and n≈1²². Though themarginal eyelid is only approximately 2 mm thick, it comprises multiplelayers of tissue with different compositions and heterogeneousvasculature. The anterior surface is skin, underneath which is found theorbicularis muscle. Beneath this is the tarsal plate, composed offibrous tissue that provides structural integrity to the eyelid. Theremay be minimal development of subcutaneous fat, and hence the eyelid iscomposed of muscle, skin, and fibrous tissue.

The muscle and fibrous regions of the eyelid have extensive arterialblood supply along both the superior and inferior margins, which maymotivate the transducer placement. Blood perfusion may a factor inhyperthermia, removing excess heat in tissue with elevated temperatureswith respect to the core blood temperature T_(c). This cooling term fora tissue at temperature T may be modeled by:

Q _(b) =−wp _(b) c _(b)(T−T _(c))  (7)

where w is an effective blood perfusion rate, and p_(b) and c_(b) arethe density and specific heat of blood, respectively.

Together with heat diffusion, the terms in equations 5 and 7 yield thebioheat transfer equation for the tissue temperature T as

$\begin{matrix}{\overset{.}{T} = {\frac{1}{pc}\left\{ {{k{\nabla^{2}T}} + {\overset{.}{Q}}_{b} + {\overset{.}{Q}}_{a}} \right\}}} & (8)\end{matrix}$

where p, c and k are the density, specific heat, and thermalconductivity of tissue, respectively. Due to the inherent attenuation inthe contact lens and epoxy materials, the ultrasonic field is attenuatedbefore reaching the tarsus. As such, the epoxy and lens increase intemperature during treatment. The heat produced within the lens isconducted towards the tissue via the gradient ∇²T in addition to {dotover (Q)}_(a).

The blood perfusion in equation 7 may be a factor motivating thesub-tarsal transducer placement due to the physiology of the eyelid. Themarginal eyelid is only approximately 2 mm thick, but comprises multiplelayers of tissue with different compositions and heterogeneousvasculature. The anterior surface is skin, underneath which is found theorbicularis muscle. Beneath this is the tarsal plate, composed offibrous tissue that provides structural integrity to the eyelid.

Blood perfusion from the subcutaneous arterial supply limits thetemperature rise that can be achieved during thermal equilibrium fromexternal heating, since the excess heat is quickly removed.

A study of the temperature difference between anterior and posteriorsurfaces of the eyelid during hyperthermia has been shown to be around 2degrees Celsius, implying that the desired equilibrium temperature of 41Celsius in the tarsus brings the anterior eyelid surface very close tothe threshold of thermal damage. Heating directly from the conjunctivalsurface tarsal plate may mitigate this risk.

Since the Meibomian glands are within approximately 1 mm of the tarsallens face, a high frequency may be used in order to optimally depositacoustic power at the tarsus, as seen from equation 6. Combining anintensity loss with the inherent attenuation of the epoxy and lensmaterial, a high frequency transducer may deposit the majority of itsenergy within the tarsus.

FIG. 26 illustrates a graph from measured attenuation of porcine eyelidwith a broadband 15 MHz transducer for an illustrative experiment.Histogram samples were taken from 126 evenly-spaced points over an 18 mmlateral sweep of the 4.0 plus/minus 0.5 thick marginal eyelid. Thestandard deviation about the mean is shown in the dashed lines.

Due to the inherent attenuation in contact lens and epoxy materials, theultrasonic field is attenuated before reaching the tarsus and that heatis produced in the lens itself. The initial heating within the eyelidhas two components: conductive and ultrasonic.

Intense heating in the cornea may cause corneal deformation, affectingor impairing vision. The cornea and humour have no vasculature, and maybe more susceptible to thermal gradients arising in ultrasound fieldswithout direct blood perfusion. A concern is to establish a safe limitof clinical temperature rise in the cornea. A conservative limit may be40 degrees Celsius. This may correspond to a maximum 6 degrees Celsiusrise, given an example resting ocular surface temperatures. The eyelidhas one of the most dense vascular anastamoses in the body, removingheat as in equation 7 and decreasing the risk of thermal burn.Furthermore, the threshold of pain and thermal damage at prolongedexposure in tissue is 45 celsius, which may be beyond the target rangeof the device. A measurement device may monitor temperatures and triggerautomatic shut-off, automatic temperature decrease, and other safetymechanisms. Since uncomfortable temperatures can be reported by apatient during treatment, this upper bound may be considered relativelybenign.

The internal air gap may serve two purposes for the safety of thedevice. First, it may provide an air backing layer to the transducer,thereby reflecting essentially all of the acoustic energy along theforward axis due to the impedance mismatch between the piezoelectricmaterial and air. This may minimize the ultrasonic pressure fieldpropagated through the scleral surface into the cornea: any pressurewave must be carried as a surface wave through the lens material,removing the risk that a direct, high intensity field would causeunwanted heating.

The air gap further acts as an insulating layer between the tarsal andcorneal faces; when the epoxy binding the transducer to the tarsal faceposterior heats due to its acoustic absorbance, heat cannot be directlyconducted between the two lens faces. Heat at the tarsal face mustdiffuse through the connecting periphery of the lenses overtop thesclera before reaching the cornea, since the air gap is largest overtopthe corneal apex. The convective mechanism of heat transfer throughstationary air is orders of magnitude lower than direct conduction,minimizing the amount of heat directly conveyed to the cornea.

Embodiments have been implemented as experimental methods, asillustrative, non-limiting examples.

A prototype of the hyperthermia device was constructed from two largescleral lenses composed of fluorosilicone acrylate. The base diametersof both were 22 mm, lathed with optical precision. The combined heightof the two scelaral lenses mounted atop each other, approximatelycoaligned, was 10.19 plus/minus 0.01 mm, leaving over 2 mm of clearancebetween the posterior of the tarsal face and the anterior of the cornealface. The contact lenses employed in this prototype have identical orsimilar base diameters and similar scleral mounting curves, and hencewhen the tarsal lens is mounted atop the corneal lens, the point ofcontact between them is near the corneal limbus, illustrated in FIG. 22,FIG. 24, FIG. 25. This point is termed the limbal point and was measuredas 6.5 plus/minus 0.1 mm, with slight variations around thecircumference.

Lens schematic and dimensions are examples only, and shows the air gapsize and limbal mounting radius. Dimensions in millimetres are shown,but not drawn to scale.

A PZT piston transducer with radius 3.25 plus/minus 0.01 mm was milledin-house with a diamond end mill from 208 plus/minus 2 mm thickpiezoceramic sheets precoated with gold electrodes. Leads from a 440 mmcoaxial cable were soldered with 350 mm solder spheres at the transducerperiphery for minimal interference with the beam. The measured centrefrequency was 11 MHz.

To attach the transducer to the posterior tarsal face, a through-holewas lathed near the apex of the tarsal lens and the transducer cable wasfed through, allowing the piston to rest inside the concave region inthe lens posterior, with approximately one mm of clearance. While thelens was oriented downwards, the transducer was secured to the posteriorof the tarsal lens by the injection of low viscosity epoxy into theclearance space between the transducer and lens via a one ml syringe andfine gauge needle. Care was taken to fill the concavity steadily tominimize the formation of bubbles within the epoxy solution, and avoidany epoxy from contacting the back face of the transducer. The epoxy wasthen cured at 45 degrees Celsius for several hours. The through-hole wassubsequently sealed airtight with epoxy using the same technique andsimilarly cured. Finally, the two lenses were epoxied together to form asingle lens with an air gap. This is an example construction for theexperiment and there may be multiple variations. The final size of theair gap may be between 1-1.5 mm at the apex of the corneal face,increasing with radial distance.

The properties of the lens were measured using a bulk cylindrical massof fluorosilicone acrylate. The speed of sound and attenuation at 11 MHzwere computed using time of flight measurements from reflections off ofa quartz plate. The attenuation shown for the epoxy was measured at 30MHz, and hence is substantially higher than expected at 11 MHz; if alinear frequency dependence is assumed in equation 6, the attenuation at11 MHz would be a third of this value at approximately 5 dB/mm.

To evaluate the ability of the internal air gap to reflect ultrasonicenergy away from the cornea, the acoustic field intensity at theposterior of the device's corneal face was measured with respect to thefield at the anterior tarsal face. As in FIG. 27, the lens transducerwas held in a water tank with a 10.5 MHz broadband composite transducer,fabricated in-house, used as a receiver. The receiver was mounted on amicrometer stage with three degrees of freedom such that the receiveraxis was approximately coaligned with the lens transducer axis, andcould be swept across the lens face in the vertical and lateraldirections. Two experiments were conducted: first, as in FIG. 27 fororientation the device was oriented with the tarsal face towards thereceiver; and second, as in orientation, with the active face directeddownwards to the rubber absorber, and corneal face exposed to thereceiver. The same vertical distance was maintained between the apex ofboth lens faces and the receiver (corresponding to a time delay of 13 μsto reach the receiver). To excite the device transducer, a 5 cycle 11MHz pulse was generated using an arbitrary waveform generator andamplified by a radiofrequency power amplifier. This pulse was thenapplied across the transducer terminals with a delay of 10 ms betweenexcitations. A short pulse may avoid producing a standing wave betweenthe receiver and lens. The signal measured by the receiver wasamplified, digitized by an oscilloscope and stored on a computer.

To correctly position the receiver over the lens apex, pulse-echomeasurements from the receiver were used, knowing that the time delaywas a minimum at tarsal face's highest point, and was a maximum at thecorneal face's lowest point.

The time-of-flight measurements also yielded the distance from thetransducer. Once positioned vertically over the corneal face, thepulse-echo measurements were ceased, and receiver was kept at a constantheight and swept laterally across the lens to measure the ultrasonicintensity of the device transducer's excitation.

The measured intensities of the field at the posterior corneal lens werethen compared with measurements of the intensity at the anterior tarsalface. The intensities of the A-lines measured from the tarsal facevaried little with vertical distance in the 10-15 μs region, which iswell within the nearfield distance of α² f/1500 approximately 7.75 cm.

The hyperthermia device was tested on a porcine subject in vivo todemonstrate its clinical potential by measuring the temperature riseinduced in both the eyelid and cornea.

Pig models are routinely used as ocular models in preclinical studiesdue to the relative similarity between human and porcine corneal tissue.The porcine cornea is 800 μs thick compared to the human thickness 500μs, and has nearly identical acoustic absorption and celerity. Theultrasonic attenuation and celerity of the scleras of both species havealso been demonstrated to be similar.

To measure the induced temperature rise in porcine tissue, type Ethermocouples were selected with a wire diameter of 130 plus/minus 1 μm.The wires were coated in Teflon insulation of thickness 85 plus/minus 1μm, and were sealed in a Teflon sheath of thickness 59 plus/minus 3 μmfor a total outer diameter of 410 plus/minus 10 μm. The thermocouplejunctions, however, were bare: the insulation and sheath were peeledback to expose the wire for 1.5 plus/minus 0.1 mm and 2.1 plus/minus 0.1mm from the junction tip for the thermocouples used in the humour andeyelid, respectively.

A 22 kg male Yorkshire pig was sedated with a 1.2 ml cocktail ofDexdomitor/Atropine and anaesthetized with 2% inhalant Isoflurane. Itscore temperature was measured with a rectal thermometer as 36.75plus/minus 0.05 degrees Celsius. The pig was placed on its right ventralside, exposing the left eye.

As shown in FIG. 28 the in-lens transducer device was placed overtop theeye such that the visual axis of the cornea and the transducer axis wereapproximately coaligned. The eyelids were pulled overtop the tarsal faceof the device and secured in place with medical tape, allowing thetransducer cable to exit the palpebral fissure near the lateral canthus.Two thermocouples were embedded in the pig tissue: one within theaqueous humour, and the other in the superior eyelid, 2-3 mm above themargin. Both thermocouples were embedded by placing them within thecannula of a 19 gauge needle, and subsequently retracting the needle toleave the thermojunction in place.

To produce hyperthermia, an 11 MHz waveform with 10% duty cycle and18.12 μs pulse width (corresponding to 200 cycles) was generated with awaveform generator and amplified by a radiofrequency power amplifier andapplied across the transducer terminals. Sonication occurred until theeyelid tissue reached steady state conditions at an elevatedtemperature, at which point the power was ceased and the tissue was leftto return to equilibrium at basal temperature. The temperatures measuredby the thermocouples throughout sonication and cooling were recordedcontinuously, and digitized with a cold-junction reference with asampling period of 100 ms. The digital values were stored on a portablecomputer in the operating room.

The thermocouples were embedded into the porcine eyelid and anteriorchamber in two sets of hyperthermia experiments. In the first set, thethermocouple in the eyelid was embedded in the eyelid at a depth of 1-2mm from the dermis in a perpendicular orientation relative to thetransducer axis, as in (A) of the FIG. 28 inset. Four hyperthermiatrials were conducted on this set; in each, sonication was applied for15 minutes. At approximately 150 minutes after the first sonicationtrial, the eyelid thermocouple was removed from the eyelid tissue andre-embedded in the superior eyelid, again several millimetres above themargin at a depth of 1-2 mm, displaced laterally from the previouspuncture site by several millimetres. In this set, however, thethermojunction orientation was parallel relative to the transducer axis,as in (B) of the inset of FIG. 28. With this orientation, three trialswere conducted, lasting 9, 15, and 15 minutes, respectively. Shortlyafter the final trial, the pig died without intervention from theeffects of anaesthesia. The thermocouple in the anterior chamber waslocated approximated 1 mm behind the cornea and kept in the samelocation during both experiment sets.

Hereafter, the two sets of trials will be referred to as perpendicularand parallel, respectively. These two orientations were chosen in orderto identify evidence of temperature artifacts induced by thethermocouples in the ultrasound field, since it has been establishedthat orientation is a factor in the magnitude of the artifact.

The computed field intensities at both the tarsal and corneal faces inthe near-field of the lens transducer are shown in FIGS. 29 a and 29 b,respectively. To calculate the relative power intensity, the maximumA-line amplitude measured in the near-field of the tarsal face has beenused as a reference; the ratio to this of A-line amplitude peaks at eachlateral position in both the tarsal and corneal near-field have beenused to approximate the relative intensity loss using the ratio to themaximum value measured.

The tarsal intensity in FIG. 29 a is constant over the piston transducerface (a=3.25 mm). In subplot FIG. 29 b, there may be evidence of pulsetransmission near the limbal contact region of the lens, at radiigreater than 6 mm. The attenuation of this pulse may be greater than 13dB. The transmitted power through the corneal face is not constant alongits circumference; the values shown in FIG. 29 b are a maximum. FIG. 29a illustrates the relative field intensity of the lens transducer facein the near-field. The dropoff occurs shortly after 4 mm in the radialdirection. FIG. 29 b illustrates relative radial intensity at theposterior of the corneal face of the lens transducer. The receiver waspositioned at a constant height above the lens 13.0 plus/minus 0.1 μsaway in time) and swept across the lens radially from the epicentre. Theintensities are relative to the maximum intensity measured at the tarsalface.

To show the general heating profiles over time, FIG. 30 a is a plot ofthe absolute temperature of the humour and eyelid during the two sets oftrials. Four hyperthermia trials were performed with the eyelidthermocouple in the perpendicular orientation, shown to the left of thevertical dashed line in FIG. 30 a. The three heating curves to the rightshow the temperature rise induced with the eyelid thermocouple in theparallel orientation.

There are several observations to make concerning this plot: (a) Thebasal temperature of the tissue (equilibrium temperature during periodsof no sonication) decreases over time for a given orientation. This isshown more clearly in FIG. 30 b, where the equilibrium temperatures havebeen computed by averaging 100 seconds of the recorded temperaturebefore each hyperthermia cycle began; (b) The temperature differenceinduced in each trial increases monotonically within the two sets; (c)There is some degree of biological noise in the system, culminating influctuations in temperature of 0.25 degree Celsius—of far largermagnitude than the electrical noise in the thermocouples. These mildlyperiodic fluctuations were observed even in equilibrium, and decreasedin frequency and magnitude once the pig was artificially ventilated at45 min after the first sonication. The fluctuations are present in boththe eyelid and humour thermocouple data.

FIG. 30 a illustrates heating curves of the humour and eyelid in eachhyperthermia trial over elapsed time from the first sonication. FIG. 30b illustrates basal temperature of the eyelid and humour over time, ascomputed from 100s of equilibrium temperatures when no ultrasound wasapplied to the tissue. Error bars show the standard deviation about themean.

The relative temperature rises ΔT over time for each trial have beensuperimposed in FIGS. 30 a and 30 b and FIGS. 31 a and 31 b which maydemonstrate the degree and rate of hyperthermia. In both of thesefigures, FIGS. 30 a and 31 a show the measured rise in the eyelid, andFIGS. 31 a and 31 b show that in the humour. Both of these plots showthe typical exponential rise and fall, with steady-state rise in theeyelid in the range of 5-8 Celsius. In the perpendicular orientation,the temperature rise in the cornea remains under 1.5 degree Celsius forall trials. For the parallel case, the corneal temperature rise did notexceed 2 degree Celsius. In the insets of these figures, a magnificationof the temperature rise after initial sonication is shown, with thescale in seconds. There is little to no thermal delay in either theeyelid or humour heating profiles: once ultrasonic power is applied, thetemperature rises almost linearly, as is expected from equation 5 beforethe effects of blood perfusion and diffusion become pronounced fromgreater ΔT. This shows that ultrasonic energy reaches the humour as wellas the cornea, however the magnitude of the temperature rise achieved inthe humour is less than a quarter of that in the eyelid.

To examine the nature of the increasing temperature rise with time, inFIGS. 33 a and 33 b the temperature rise in the eyelid is plottedagainst the elapsed time since the first sonication.

Subplots FIGS. 33 a and 33 b show the steady-state ΔT reached for theeyelid and cornea, respectively. The four leftmost curves in bothsubplots show the rise in the perpendicular thermocouple orientation,and the three rightmost curves show the parallel orientation.

The mean values for ΔT were computed from the latter ½ of the heatingcurve before sonication ceased, and the error bars show the standarddeviation about the mean for this value. In both experiment sets in FIG.33 a, there is a linear increase in ΔT in the eyelid with time, howeverthe increase is not monotonic with elapsed experiment time: once thethermocouple was removed from the orbicularis and again embedded in adifferent position, the temperature gain was reduced to 5 degreeCelsius—nearly the elevation obtained in the first trial for theperpendicular orientation. Furthermore, the slope of the equilibriumtemperature line in FIG. 33 a is approximately half that of FIG. 33 bthe increase in ΔT occurs far faster than before.

The ΔT curves for the humour plotted in FIG. 33 b show similar trendswith time, but there is a notable difference in that the drop in ΔTbetween the perpendicular and parallel sets of trials is far lesspronounced. Unlike the eyelid in subplot FIG. 33 a, the humour ΔT forthe first parallel experiment does not return to lower value similar inmagnitude to the first trial of the perpendicular experiment. Though thetemperature rise is lesser, it is comparable to the values measured inthe two prior perpendicular trials. Furthermore, it should be noted thatthe first parallel trial was conduced for only 9 minutes, while theother trials were conducted for over 15 minutes. Hence, the steady staterise for the first parallel trial is an underestimate, though sincesteady state conditions appear to be reached shortly after 5 minutes ofsonication in all trials, this is likely a minor deviation.

FIGS. 33 a and 33 b illustrate temperature rise over elapsed time sincethe initial sonication, measured in the FIG. 33 a eyelid and FIG. 33 baqueous humour. The heating profiles in the unbroken, black lines showthe rises from initial equilibrium temperatures, while the red dashedline shows the equilibrium temperatures, computed from the mean of thelatter ½ of the heating curve, when steady-state was reached. Error barsshow the standard deviation about this mean value. Note the scaledifference in the two subplots.

Embodiments described herein may measure temperature during ultrasoundhyperthermia with embedded thermocouples. When a pressure wave impingesupon a bare thermocouple, the viscous shear forces acting between thewire and the medium produce local heating at the junction may cause atemperature artifact and yielding a measurement greater than if thethermocouple were absent. Calculations may automatically adjust tocorrect this artifact. The magnitude of this artifact depends on severalfactors: the orientation of the wire with respect to the wavepropagation direction, the wire diameter, and the presence of insulatingcoatings that attenuate the ultrasonic field. Embodiments may minimizethe wire diameter with respect to the field wavelength, using onlyunsheathed wires, and orienting the wires in the direction of wavepropagation.

There are several telltale signs of artifacts in the heating curves: themoment sonication begins, an initial temperature jump may occur withinthe first few hundreds milliseconds. When sonication ceases, therecorded temperature drops suddenly by −T₀ before continuing to decreaseexponentially, allowing T₀ to be estimated by backwards extrapolation.The magnitude of T₀ is reported to be as large as 1 degree Celsius inporcine muscle just below the skin for 18-30 kg animals, as well as forthermocouples in polyurethane-coated catheters in humans.

The sudden rise and fall by T₀ was not observed in any of the trials ineither orientation in the present work. Since the thermocouple digitizerhad a sampling period of 100 ms, this is a sufficient resolution todetect a rapid change within several hundred milliseconds. There wasalso no observed systematic difference in temperature rise introduced bythe thermocouple orientation, which would have been expected if theartifact were significant. It is thought likely that any artifacts, ifpresent, were negligible in our experiments for three example reasons:the thermocouples used had bare wire thermojunctions in order to avoidthe large artefacts previously reported with Teflon sheathing; whilemost work examining the effect of viscous heating has been down forfocused beams, the configuration of interest is and diffuse due to theconvex geometry of the lens and piston transducer; hence the acousticwave impinging upon the thermocouple is of a lesser intensity thanpreviously considered in literature.

Attenuation of epoxy (˜5 dB/mm) in combination with the high attenuationof porcine eyelid (˜3 dB/mm) at 11 MHz further reduces the intensity. Asa loss of 8 dB after 1 mm of the tarsus corresponds to only 40% of theenergy remaining as a propagating wave.

To investigate the increase in temperature rise seen in FIGS. 33 a and33 b, the effective blood perfusion was calculated for each trial. Fromequation 8, in steady state conditions before sonication ceases, T=0 and∇²T is assumed to be small once thermal equilibrium has been reached.Hence the solution of T once the ultrasonic power is turned off is anexponential decay with a known form from equation 7 as

$\begin{matrix}{T = {T_{c} + {\left( {T_{i} - T_{c}} \right)\exp \left\{ {{- w}\frac{p_{b}c_{b}}{pc}t} \right\}}}} & (9)\end{matrix}$

where T_(i) is the tissue temperature when the power ceasesT_(i)−T_(c)=ΔT. Hence w may be determined from a least-squaresregression of a plot of T−T_(c) against time. This method provides anoverestimate of the blood perfusion, particularly in the eyelid due toits relatively large surface area per mass, since heat exchange withambient air contributes to the cooling. This term has an identical formto equation 7, however, the coefficient of heat transfer with static airis generally small.

The effective perfusion was determined in this manner for temperaturemeasurements in the eyelid, using the equilibrium temperature beforeeach trial as T_(c). Only the temperature data from the eyelidthermocouple were considered, since the cornea and aqueous humour haveno vasculature, and are cooled by heat diffusion alone. Sample plots ofT−T_(c) over relaxation time to demonstrate the fit to the exponentialdecay are shown in FIGS. 34 a and 34 b. To estimate the uncertainty inthis numerical method, a moving window of 20 s duration was used tocompute the slope, with starting times in the range of 10 to 50 secondsafter sonication ceased. The final perfusion value was then determinedfrom a least-squares regression and averaged over all computations withcoefficients of determination r² greater than 0.995. Thus theuncertainty was estimated using the standard deviation about the meanperfusion value.

Table 5 may illustrate example profusion rates for the eyelid withthermocouple for use in FIGS. 34 a and b.

TABLE 5 Trial w (ml/min/100 g) Porp. 1 89 ± 2 2 75 ± 1 3 80 ± 3 4 69 ± 2Par. 1 81 ± 2 2 57 ± 4 3 51 ± 2

In computing w the numerical values for the biological parameters were:p=1090 kg/m³, c=3530 J/kg/K, p_(b)=1060 kg/m³, and c_(b)=3900 J/kg/K.Effective perfusion values differ greatly between different tissues.

Example perfusion rates of have been plotted over elapsed time sincepuncturing the eyelid in FIG. 35 to examine their time dependence. Thebottom x-axis (black) shows the elapsed time since puncturing the eyelidin the perpendicular set of trials, and the top x-axis (red) shows theelapsed time since puncture in the parallel set. The dual-axis is toallow a view of the perfusion over the entire experiment, while bearingin mind that the thermocouple in the eyelid was removed and thenembedded once more after about 150 min. Over elapsed experiment time,the eyelid perfusion has a general downward trend, if the suddenincrease in perfusion after puncturing the orbicularis anew is treatedas extraneous (naturally, a puncture wound produces a higher localperfusion). The effective perfusion rates do not correlate perfectlywith the temperature rises observed throughout the respective trials asshown in FIGS. 33 a and 33 b. However, the decrease in w over timethroughout each set of trials is expected for increasing ΔT according toequation 8, assuming no change in the thermal diffusivity throughout theporcine tissue.

FIG. 35 shows computed effective blood perfusion rates in the eyelid forthe two sets of trials over elapsed time since puncturing theorbicularis in the perpendicular and parallel experiments. Error barsshow the standard deviation about the mean value computed from multiplewindows in time.

There are biological factors to consider that may affect both thetemperature rise and the perfusion rates. For one, prolonged anaesthesiadepresses heart and breathing rates. If the basal corneal temperaturesin FIG. 30 b are an indicator of the core temperature, they show thatthe physiological effects of anaesthesia are pronounced over time. It isalso intuitive to expect that the initial biological response ofpiercing the eyelid with a needle affects the perfusion in the vicinityof the puncture wound. The initial bleeding from damaged vasculature andsubsequent localized blood coagulation and clot formation may change theultrasonic absorption or heat capacity of the tissue. The lack of aclear correlation between the perfusion and the temperature risesachieved lead us to believe that other biological responses affect thesteady state temperature.

FIG. 36 shows the temperature rises plotted against the equilibriumtemperature immediately before sonication for all trials in the eyelid(FIG. 36 a) and humour (FIG. 36 b). Decreasing basal temperature beforesonication is related to the magnitude of ΔT, as evidenced by thecomputed Pearson correlation coefficients r, shown in the top rightcorner of the plots.

FIG. 36 shows temperature rise correlated with basal temperature in forthe eyelid (FIG. 36 a), and humour (FIG. 36 b). The pearson correlationcoefficient r is shown at the top right for both perpendicular andparallel trials combined. The strong negative correlation indicated bythese r values suggests that basal temperature is a factor in themagnitude of the observed ΔT.

The primary aim of hyperthermia therapy for treating obstructiveMeibomian Gland Dysfunction is to liquify the keratinized meibum withinthe meibomian glands. An example temperature regime is a 5-7 degreesCelsius rise, which raises the glands' temperature to 41-43 degreesCelsius. In FIG. 33, the increasing ΔT over time is thought to be theproduct of the biological effects of prolonged anaesthesia, decreasingbasal temperature, and blood perfusion.

The safety of the cornea is a factor; the temperature rise within itshould be as low as reasonably possible, not exceeding 6 degreesCelsius, for example.

In FIG. 29( b), the ultrasonic field intensity at the corneal face ofthe lens was found to be more than 13 dB weaker than the field measuredat the tarsal face. This corresponds to less than a quarter of theenergy transmitted at the limbal point in FIG. 29( b). That acousticfields are produced at the corneal face is confirmed by the shape of thehyperthermia curves in FIGS. 31 a and 31 b: both subplots of the (a)eyelid and (b) cornea have the similar heating and coolingcharacteristics. However, while ultrasound is reaching the aqueoushumour, it has only a minor effect on the corneal temperature: notemperature rise greater than 2 degrees Celsius was observed, and allbut one of the hyperthermia trials were below 1.5 degree Celsius duringsteady state conditions. The heating observed in the cornea wasgenerally less than a quarter of that measured in the eyelid, whichagrees with the relative energy deposition when the higher acousticattenuation of the eyelid is taken into consideration. Naturally, inmaking measurements of the aqueous humour in the anterior chamber, theassumption that the humour is in thermal equilibrium with the corneamust be stressed. While the cornea is in direct contact with the tarsallens, the assumption of thermal equilibrium is thought reasonable, sincethe cornea may be composed of nearly 80% water.

The meibomian glands may be located along the entire length of themarginal eyelid—a length of about 25 mm. The piston transducer of theexample prototype has a radius of only 3.25 mm. A larger radius may alsobe used in some examples. The field intensity in FIGS. 29 a and 29 b maydecline steeply to −6 dB beyond 4 mm radially outward from thetransducer centre: thus the prototype applies direct heat to only athird of the meibomian glands located at the centre of the superior andinferior eyelid margins. The remedy for this may be the design of alimbal point located farther from the epicentre of the lens, allowingfor a larger diameter transducer to be contained within the lens. Whilesuch a design may be unable to directly heat the entire length of themargin, heat diffusion radially outwards will aid in the heating of themeibomian glands located near the lateral and medial canthi. Otherdesigns and dimensions may be used and these are examples only.

This is an example prototype design for an ultrasonic device for thehyperthermia treatment of obstructive MGD, other variants may also beused. The example device may include of a piezoelectric transducercontained within a contact lens with an internal air gap, such that thetwo faces of the lens abut the tarsus and the sclera, and the transduceris mechanically fixed to the posterior tarsal face, such that the airgap provides the transducer with an air backing. This reflects acousticwaves towards the tarsus and away from the cornea, preventing cornealtemperature elevation from direct ultrasound. The target heating in theeyelid may be 5-7 degrees Celsius, with minimal corneal temperaturerise. This an example range and other temperature targets may be used inaccordance with modified treatment parameters.

Further, the transducer may be separate from the lens as describedherein and in some embodiments may not be located within the chamber ofair of the air gap lens.

The example prototype of this design may be constructed from contactlenses and a PZT piston transducer of radius 3.25 mm, as a non-limitingillustrative experimental example. Field intensity measurements showedthat the air gap was effective at preventing direct ultrasonictransmission into the corneal apex, though some acoustic energy at −13dB was detectable at the limbal point where the two contact lenses wereepoxied. In an in vivo experiment on a porcine subject, it was foundthat a 5-8 degrees Celsius equilibrium temperature rise in the eyelidmay be achievable in a clinical timeframe of 10-15 minutes. During thistime, the corneal temperature did not rise more than 2 degrees Celsius,which is well within the established safety limits of <40 degreesCelsius. The temperature curves obtained from the bare wirethermocouples used in the experiment were examined for evidence oftemperature artifacts, though none of the telltale signs were observed.However, a general increase in temperature rise over experimental timewas noted. Analysis of the blood perfusion in the eyelid may show thatit may decrease with time, but that puncturing the eyelid increased theperfusion immediately afterward. The increasing temperature rises alsocorrelated with a decreasing basal temperature of the eyelid and humour.Hence it is thought likely that biological factors associated withanaesthesia and piercing the eyelid and embedding the thermocouple mayimpact the results.

Other examples embodiments may involve refinement of the exampleprototype and extended testing. A device constructed from custom lensesmay allow for a transducer with a larger surface area, targeting agreater portion of the meibomian glands along the length of the eyelidmargins. A separate lens and transducer system may also allow for atransducer with a larger surface area. In some examples, infraredthermography may be used to measure the eyelid surface temperature,which may eliminate the biological effects of embedding the thermocouplewithin the eyelid. Though thermography may detect the surfacetemperature of the eyelid, this may give a lower bound on thetemperature of the tarsus, and an upper bound may be may be approximatedfrom thermal models of the tissue in conjunction with thesemeasurements.

Embodiments have been described by way of example only, and variousmodification and variations may be made to these exemplary embodiments.

1. The use of an air gap lens and an ultrasound device configured fortreatment of an eye condition, wherein the device comprises at least oneultrasound transducer for supplying ultrasound waves to an areaproximate to the portion of the eyelid according to treatmentparameters, wherein the air gap lens protects ocular tissue of the eye,wherein the air gap lens comprises lens layers and a chamber of air. 2.The use of claim 1, wherein the at least one ultrasound transducer ispositioned within the internal chamber of air.
 3. The use of claim 1,wherein the at least one ultrasound transducer is separate from the airgap lens.
 4. The use of claim 1, wherein the one ultrasound transduceris of a longer length than the air gap lens.
 5. The use of claim 1,wherein the ultrasound transducer comprises polyvinylidene fluoridefilm.
 6. An air gap lens for treating an eye condition, wherein the airgap lens comprises lens layers and an internal chamber of air, whereinat least one ultrasound transducer supplies ultrasound waves to an areaproximate to a portion of an eyelid according to treatment parameters,wherein the air gap lens protects ocular tissue of the eye.
 7. The airgap lens of claim 6, wherein the ultrasound transducer is positionedwithin the internal chamber of air.
 8. The air gap lens of claim 6,wherein the air gap lens is of a shorter length than the one ultrasoundtransducer.
 9. The air gap lens of claim 6, wherein the air gap servesas an air backing to the ultrasound transducer to prevent acousticenergy from directly reaching the cornea of the eye.
 10. The air gaplens of claim 6, further comprising an absorptive material to blockpenetration of ocular tissue by the ultrasound waves.
 11. The air gaplens of claim 6, wherein the chamber of air blocks penetration of oculartissue by the ultrasound waves.
 12. A system for treating an eyecondition comprising: an ultrasound device comprising at least oneultrasound transducer for supplying ultrasound waves to an areaproximate to a portion of the eyelid according to treatment parameters;and an air gap lens to protect ocular tissue of the eye, wherein thelens is configured to form a chamber of air between lens layers.
 13. Thesystem of claim 12, wherein the ultrasound transducer is separate fromthe air gap lens.
 14. The system of claim 12, wherein the one ultrasoundtransducer is of a longer length than the air gap lens.
 15. The systemof claim 12, wherein the ultrasound transducer comprises polyvinylidenefluoride film.
 16. The system of claim 12, wherein the ultrasoundtransducer is a PZT transducer.
 17. The system of claim 12, wherein thelens comprises an absorptive material to block penetration of oculartissue by the ultrasound waves.
 18. The system of claim 12, wherein thechamber of air blocks penetration of ocular tissue by the ultrasoundwaves.
 19. The system of claim 12, further comprising a lens speculum toelevate the eyelid from the eye globe and create an airspace between eyeglobe and eyelid.
 20. The system of claim 12, further comprising atemperature measurement mechanism for measuring the temperature of thearea proximate to the portion of the eyelid, wherein the temperaturemeasurement mechanism comprises a thermal couple, wherein the thermalcouple is positioned on or within the air gap lens.
 21. The system ofclaim 12, wherein the at least one ultrasound transducer provides atreatment frequency ranging from 0.2 to 10 MHz.
 22. The system of claim12, wherein the ultrasound transducer is positioned within the internalchamber of air.